International Journal of Molecular Sciences

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16 pages, 999 KiB

Open AccessArticle

Contribution of the Tyr-1 in Plantaricin149a to Disrupt Phospholipid Model Membranes

by José L. S. Lopes, Maria J. Gómara, Isabel Haro, Georgina Tonarelli and Leila M. Beltramini

Int. J. Mol. Sci. 2013, 14(6), 12313-12328; https://doi.org/10.3390/ijms140612313 - 7 Jun 2013

Cited by 8 | Viewed by 6910

Abstract

Plantaricin149a (Pln149a) is a cationic antimicrobial peptide, which was suggested to cause membrane destabilization via the carpet mechanism. The mode of action proposed to this antimicrobial peptide describes the induction of an amphipathic α-helix from Ala7 to Lys20, while the N-terminus residues [...] Read more.

Plantaricin149a (Pln149a) is a cationic antimicrobial peptide, which was suggested to cause membrane destabilization via the carpet mechanism. The mode of action proposed to this antimicrobial peptide describes the induction of an amphipathic α-helix from Ala7 to Lys20, while the N-terminus residues remain in a coil conformation after binding. To better investigate this assumption, the purpose of this study was to determine the contributions of the Tyr1 in Pln149a in the binding to model membranes to promote its destabilization. The Tyr to Ser substitution increased the dissociation constant (K_D) of the antimicrobial peptide from the liposomes (approximately three-fold higher), and decreased the enthalpy of binding to anionic vesicles from −17.2 kcal/mol to −10.2 kcal/mol. The peptide adsorption/incorporation into the negatively charged lipid vesicles was less effective with the Tyr1 substitution and peptide Pln149a perturbed the liposome integrity more than the analog, Pln149S. Taken together, the peptide-lipid interactions that govern the Pln149a antimicrobial activity are found not only in the amphipathic helix, but also in the N-terminus residues, which take part in enthalpic contributions due to the allocation at a lipid-aqueous interface. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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18 pages, 2823 KiB

Open AccessArticle

Structure and Conformational Dynamics of DMPC/Dicationic Surfactant and DMPC/Dicationic Surfactant/DNA Systems

by Zuzanna Pietralik, Rafał Krzysztoń, Wojciech Kida, Weronika Andrzejewska and Maciej Kozak

Int. J. Mol. Sci. 2013, 14(4), 7642-7659; https://doi.org/10.3390/ijms14047642 - 9 Apr 2013

Cited by 29 | Viewed by 8923

Abstract

Amphiphilic dicationic surfactants, known as gemini surfactants, are currently studied for gene delivery purposes. The gemini surfactant molecule is composed of two hydrophilic “head” groups attached to hydrophobic chains and connected via molecular linker between them. The influence of different concentrations of 1,5-bis [...] Read more.

Amphiphilic dicationic surfactants, known as gemini surfactants, are currently studied for gene delivery purposes. The gemini surfactant molecule is composed of two hydrophilic “head” groups attached to hydrophobic chains and connected via molecular linker between them. The influence of different concentrations of 1,5-bis (1-imidazolilo-3-decyloxymethyl) pentane chloride (gemini surfactant) on the thermotropic phase behaviour of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers with and without the presence of DNA was investigated using Fourier transformed infrared (FTIR) and circular dichroism (CD) spectroscopies, small angle scattering of synchrotron radiation and differential scanning calorimetry. With increasing concentration of surfactant in DMPC/DNA systems, a disappearance of pretransition and a decrease in the main phase transition enthalpy and temperature were observed. The increasing intensity of diffraction peaks as a function of surfactant concentration also clearly shows the ability of the surfactant to promote the organisation of lipid bilayers in the multilayer lamellar phase. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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13 pages, 220 KiB

Open AccessArticle

Lipid Status of the Two High Latitude Fish Species, Leptoclinus maculatus and Lumpenus fabricii

by Svetlana A. Murzina, Zinaida A. Nefedova, Stig Falk-Petersen, Pauli O. Ripatti, Tatiana R. Ruokolainen, Svetlana N. Pekkoeva and Nina N. Nemova

Int. J. Mol. Sci. 2013, 14(4), 7048-7060; https://doi.org/10.3390/ijms14047048 - 27 Mar 2013

Cited by 22 | Viewed by 7001

Abstract

A comparative study of the lipid status (i.e., the total lipid and phospholipid concentrations and the percentage of fatty acids of the total lipids) of adult specimens of daubed shanny (Leptoclinus maculatus) from Svalbard waters (Isfjord) and slender eel [...] Read more.

A comparative study of the lipid status (i.e., the total lipid and phospholipid concentrations and the percentage of fatty acids of the total lipids) of adult specimens of daubed shanny (Leptoclinus maculatus) from Svalbard waters (Isfjord) and slender eel blenny (Lumpenus fabricii) from the White Sea (Onega Bay and Tersky shore) was performed to study the metabolism and functions of lipids of these fishes in ontogeny and under various ecological conditions. Slender eel blenny from both areas of the White Sea were distinguished by a high level of sphingomyelin compared with the daubed shanny from Svalbard, and the amount of total phospholipids was higher in slender eel blenny from Onega Bay than in slender eel blenny from the Tersky shore. The extent of saturation and the signature of polyenic fatty acids varied according to the specific species of the Stichaeidae family under study. These results demonstrate the differences in the trophoecological and hydrobiological conditions of habitations of these species and highlighted the importance of considering certain trends in the lipid profiles of these fishes as specific features of the organization of the ecological and biochemical mechanisms of adaptation. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

20 pages, 967 KiB

Open AccessArticle

Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease

by Marcus O. W. Grimm, Viola J. Haupenthal, Tatjana L. Rothhaar, Valerie C. Zimmer, Sven Grösgen, Benjamin Hundsdörfer, Johannes Lehmann, Heike S. Grimm and Tobias Hartmann

Int. J. Mol. Sci. 2013, 14(3), 5879-5898; https://doi.org/10.3390/ijms14035879 - 13 Mar 2013

Cited by 34 | Viewed by 8441

Abstract

Alzheimer’s disease (AD) is characterized by extracellular accumulation of amyloid-β peptide (Aβ), generated by proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. Aβ generation is inhibited when the initial ectodomain shedding is caused by α-secretase, cleaving APP within the [...] Read more.

Alzheimer’s disease (AD) is characterized by extracellular accumulation of amyloid-β peptide (Aβ), generated by proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. Aβ generation is inhibited when the initial ectodomain shedding is caused by α-secretase, cleaving APP within the Aβ domain. Therefore, an increase in α-secretase activity is an attractive therapeutic target for AD treatment. APP and the APP-cleaving secretases are all transmembrane proteins, thus local membrane lipid composition is proposed to influence APP processing. Although several studies have focused on γ-secretase, the effect of the membrane lipid microenvironment on α-secretase is poorly understood. In the present study, we systematically investigated the effect of fatty acid (FA) acyl chain length (10:0, 12:0, 14:0, 16:0, 18:0, 20:0, 22:0, 24:0), membrane polar lipid headgroup (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine), saturation grade and the FA double-bond position on α-secretase activity. We found that α-secretase activity is significantly elevated in the presence of FAs with short chain length and in the presence of polyunsaturated FAs, whereas variations in the phospholipid headgroups, as well as the double-bond position, have little or no effect on α-secretase activity. Overall, our study shows that local lipid membrane composition can influence α-secretase activity and might have beneficial effects for AD. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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10 pages, 1096 KiB

Open AccessArticle

Interlamellar Organization of Phase Separated Domains in Multi-Component Lipid Multilayers: Energetic Considerations

by Lobat Tayebi, Atul N. Parikh and Daryoosh Vashaee

Int. J. Mol. Sci. 2013, 14(2), 3824-3833; https://doi.org/10.3390/ijms14023824 - 8 Feb 2013

Cited by 3 | Viewed by 6503

Abstract

A recent experimental study [1] has demonstrated the alignment of phase separated domains across hundreds of bilayer units in multicomponent stacked lipid bilayers. The origin of this alignment is the interlamellar coupling of laterally phase separated domains. Here, we develop a theoretical model [...] Read more.

A recent experimental study [1] has demonstrated the alignment of phase separated domains across hundreds of bilayer units in multicomponent stacked lipid bilayers. The origin of this alignment is the interlamellar coupling of laterally phase separated domains. Here, we develop a theoretical model that presents the energetics description of this phenomenon based on the minimization of the free energy of the system. Specifically, we use solution theory to estimate the competition between energy and entropy in different stacking configurations. The model furnishes an elemental phase diagram, which maps the domain distributions in terms of the strength of the intra- and inter-layer interactions and estimates the value of inter-layer coupling for complete alignment of domains in the stacks of five and ten bilayers. The area fraction occupied by co-existing phases was calculated for the system of the minimum free energy, which showed a good agreement with experimental observations. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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Graphical abstract

26 pages, 4337 KiB

Open AccessArticle

Preparation of DOPC and DPPC Supported Planar Lipid Bilayers for Atomic Force Microscopy and Atomic Force Spectroscopy

by Simon J. Attwood, Youngjik Choi and Zoya Leonenko

Int. J. Mol. Sci. 2013, 14(2), 3514-3539; https://doi.org/10.3390/ijms14023514 - 6 Feb 2013

Cited by 197 | Viewed by 17035

Abstract

Cell membranes are typically very complex, consisting of a multitude of different lipids and proteins. Supported lipid bilayers are widely used as model systems to study biological membranes. Atomic force microscopy and force spectroscopy techniques are nanoscale methods that are successfully used to [...] Read more.

Cell membranes are typically very complex, consisting of a multitude of different lipids and proteins. Supported lipid bilayers are widely used as model systems to study biological membranes. Atomic force microscopy and force spectroscopy techniques are nanoscale methods that are successfully used to study supported lipid bilayers. These methods, especially force spectroscopy, require the reliable preparation of supported lipid bilayers with extended coverage. The unreliability and a lack of a complete understanding of the vesicle fusion process though have held back progress in this promising field. We document here robust protocols for the formation of fluid phase DOPC and gel phase DPPC bilayers on mica. Insights into the most crucial experimental parameters and a comparison between DOPC and DPPC preparation are presented. Finally, we demonstrate force spectroscopy measurements on DOPC surfaces and measure rupture forces and bilayer depths that agree well with X-ray diffraction data. We also believe our approach to decomposing the force-distance curves into depth sub-components provides a more reliable method for characterising the depth of fluid phase lipid bilayers, particularly in comparison with typical image analysis approaches. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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20 pages, 4068 KiB

Open AccessArticle

Structural Characterization of an LPA₁ Second Extracellular Loop Mimetic with a Self-Assembling Coiled-Coil Folding Constraint

by John K. Young, Benjamin T. Clayton, Alexandra Kikonyogo, Truc-Chi T. Pham and Abby L. Parrill

Int. J. Mol. Sci. 2013, 14(2), 2788-2807; https://doi.org/10.3390/ijms14022788 - 29 Jan 2013

Cited by 4 | Viewed by 6740

Abstract

G protein-coupled receptor (GPCR) structures are of interest as a means to understand biological signal transduction and as tools for therapeutic discovery. The growing number of GPCR crystal structures demonstrates that the extracellular loops (EL) connecting the membrane-spanning helices show tremendous structural variability [...] Read more.

G protein-coupled receptor (GPCR) structures are of interest as a means to understand biological signal transduction and as tools for therapeutic discovery. The growing number of GPCR crystal structures demonstrates that the extracellular loops (EL) connecting the membrane-spanning helices show tremendous structural variability relative to the more structurally-conserved seven transmembrane α-helical domains. The EL of the LPA₁ receptor have not yet been conclusively resolved, and bear limited sequence identity to known structures. This study involved development of a peptide to characterize the intrinsic structure of the LPA₁ GPCR second EL. The loop was embedded between two helices that assemble into a coiled-coil, which served as a receptor-mimetic folding constraint (LPA₁-CC-EL2 peptide). The ensemble of structures from multi-dimensional NMR experiments demonstrated that a robust coiled-coil formed without noticeable deformation due to the EL2 sequence. In contrast, the EL2 sequence showed well-defined structure only near its C-terminal residues. The NMR ensemble was combined with a computational model of the LPA₁ receptor that had previously been validated. The resulting hybrid models were evaluated using docking. Nine different hybrid models interacted with LPA 18:1 as expected, based on prior mutagenesis studies, and one was additionally consistent with antagonist affinity trends. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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16 pages, 1194 KiB

Open AccessArticle

The Induction of Cytokine Release in Monocytes by Electronegative Low-Density Lipoprotein (LDL) Is Related to Its Higher Ceramide Content than Native LDL

by Montserrat Estruch, Jose Luis Sanchez-Quesada, Lorea Beloki, Jordi Ordoñez-Llanos and Sonia Benitez

Int. J. Mol. Sci. 2013, 14(2), 2601-2616; https://doi.org/10.3390/ijms14022601 - 28 Jan 2013

Cited by 24 | Viewed by 7534

Abstract

Electronegative low-density lipoprotein (LDL(−)) is a minor modified LDL subfraction that is present in blood. LDL(−) promotes inflammation and is associated with the development of atherosclerosis. We previously reported that the increase of cytokine release promoted by this lipoprotein subfraction in monocytes is [...] Read more.

Electronegative low-density lipoprotein (LDL(−)) is a minor modified LDL subfraction that is present in blood. LDL(−) promotes inflammation and is associated with the development of atherosclerosis. We previously reported that the increase of cytokine release promoted by this lipoprotein subfraction in monocytes is counteracted by high-density lipoprotein (HDL). HDL also inhibits a phospholipase C-like activity (PLC-like) intrinsic to LDL(−). The aim of this work was to assess whether the inhibition of the PLC-like activity by HDL could decrease the content of ceramide (CER) and diacylglycerol (DAG) generated in LDL(−). This knowledge would allow us to establish a relationship between these compounds and the inflammatory activity of LDL(−). LDL(−) incubated at 37 °C for 20 h increased its PLC-like activity and, subsequently, the amount of CER and DAG. We found that incubating LDL(−) with HDL decreased both products in LDL(−). Native LDL was modified by lipolysis with PLC or by incubation with CER-enriched or DAG-enriched liposomes. The increase of CER in native LDL significantly increased cytokine release, whereas the enrichment in DAG did not show these inflammatory properties. These data point to CER, a resultant product of the PLC-like activity, as a major determinant of the inflammatory activity induced by LDL(−) in monocytes. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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13 pages, 687 KiB

Open AccessArticle

Effect of Repetitive Lysine-Tryptophan Motifs on the Eukaryotic Membrane

by Ramamourthy Gopal, Jong Kook Lee, Jun Ho Lee, Young Gwon Kim, Gwang Chae Oh, Chang Ho Seo and Yoonkyung Park

Int. J. Mol. Sci. 2013, 14(1), 2190-2202; https://doi.org/10.3390/ijms14012190 - 22 Jan 2013

Cited by 14 | Viewed by 7258

Abstract

In a previous study, we synthesized a series of peptides containing simple sequence repeats, (KW)_n–NH₂ (n = 2,3,4 and 5) and determined their antimicrobial and hemolytic activities, as well as their mechanism of antimicrobial action. However, (KW)₅ [...] Read more.

In a previous study, we synthesized a series of peptides containing simple sequence repeats, (KW)_n–NH₂ (n = 2,3,4 and 5) and determined their antimicrobial and hemolytic activities, as well as their mechanism of antimicrobial action. However, (KW)₅ showed undesirable cytotoxicity against RBC cells. In order to identify the mechanisms behind the hemolytic and cytotoxic activities of (KW)₅, we measured the ability of these peptides to induce aggregation of liposomes. In addition, their binding and permeation activities were assessed by Trp fluorescence, calcein leakage and circular dichrorism using artificial phospholipids that mimic eukaryotic liposomes, including phosphatidylcholine (PC), PC/sphingomyelin (SM) (2:1, w/w) and PC/cholesterol (CH) (2:1, w/w). Experiments confirmed that only (KW)₅ induced aggregation of all liposomes; it formed much larger aggregates with PC:CH (2:1, w/w) than with PC or PC:SM (2:1, w/w). Longer peptide (KW)₅, but not (KW)₃ or (KW)₄, strongly bound and partially inserted into PC:CH compared to PC or PC:SM (2:1, w/w). Calcein release experiments showed that (KW)₅ induced calcein leakage from the eukaryotic membrane. Greater calcein leakage was induced by (KW)₅ from PC:CH than from PC:SM (2:1, w/w) or PC, whereas (KW)₄ did not induce calcein leakage from any of the liposomes. Circular dichroism measurements indicated that (KW)₅ showed higher conformational transition compared to (KW)₄ due to peptide-liposome interactions. Taken together, our results suggest that (KW)₅ reasonably mediates the aggregation and permeabilization of eukaryotic membranes, which could in turn explain why (KW)₅ displays efficient hemolytic activity. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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17 pages, 2024 KiB

Open AccessArticle

Anti-Legionella dumoffii Activity of Galleria mellonella Defensin and Apolipophorin III

by Marta Palusińska-Szysz, Agnieszka Zdybicka-Barabas, Bożena Pawlikowska-Pawlęga, Pawel Mak and Małgorzata Cytryńska

Int. J. Mol. Sci. 2012, 13(12), 17048-17064; https://doi.org/10.3390/ijms131217048 - 12 Dec 2012

Cited by 29 | Viewed by 8532

Abstract

The gram-negative bacterium Legionella dumoffii is, beside Legionella pneumophila, an etiological agent of Legionnaires’ disease, an atypical form of pneumonia. The aim of this study was to determine the antimicrobial activity of Galleria mellonella defense polypeptides against L. dumoffii. The extract [...] Read more.

The gram-negative bacterium Legionella dumoffii is, beside Legionella pneumophila, an etiological agent of Legionnaires’ disease, an atypical form of pneumonia. The aim of this study was to determine the antimicrobial activity of Galleria mellonella defense polypeptides against L. dumoffii. The extract of immune hemolymph, containing a mixture of defense peptides and proteins, exhibited a dose-dependent bactericidal effect on L. dumoffii. The bacterium appeared sensitive to a main component of the hemolymph extract, apolipophorin III, as well as to a defense peptide, Galleria defensin, used at the concentrations 0.4 mg/mL and 40 μg/mL, respectively. L. dumoffii cells cultured in the presence of choline were more susceptible to both defense factors analyzed. A transmission electron microscopy study of bacterial cells demonstrated that Galleria defensin and apolipophorin III induced irreversible cell wall damage and strong intracellular alterations, i.e., increased vacuolization, cytoplasm condensation and the appearance of electron-white spaces in electron micrographs. Our findings suggest that insects, such as G. mellonella, with their great diversity of antimicrobial factors, can serve as a rich source of compounds for the testing of Legionella susceptibility to defense-related peptides and proteins. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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18 pages, 949 KiB

Open AccessArticle

Characterization of in Vitro Modified Human Very Low-Density Lipoprotein Particles and Phospholipids by Capillary Electrophoresis

by Yi-Ning Liu, Ting-Yu Shu, Huai-Guang Xie, Wei-Ting Lai, Yi-Han Liao, Mei-Yu Su, You-Sian Lin, Yen-Yi Chen, Yi-Jyun Lin, Chin-Pong Chong and Mine-Yine Liu

Int. J. Mol. Sci. 2012, 13(12), 16400-16417; https://doi.org/10.3390/ijms131216400 - 3 Dec 2012

Cited by 3 | Viewed by 7218

Abstract

A simple capillary zone electrophoresis (CZE) method was used to characterize human very low-density lipoprotein (VLDL) particles for four healthy donors. One major peak was observed for native, in vitro oxidized and glycated VLDL particles. The effective mobilities and peak areas of the [...] Read more.

A simple capillary zone electrophoresis (CZE) method was used to characterize human very low-density lipoprotein (VLDL) particles for four healthy donors. One major peak was observed for native, in vitro oxidized and glycated VLDL particles. The effective mobilities and peak areas of the capillary electrophoresis (CE) profiles showed good reproducibility and precision. The mobility of the oxidized VLDL peak was higher than that of the native VLDL. The mobility of the glycated VLDL peak was similar to that of the native VLDL. Phospholipids isolated from VLDL particles were analyzed by our recently developed micellar electrokinetic chromatography (MEKC) with a high-salt stacking method. At absorbance 200 nm, the native VLDL phospholipids showed a major peak and a minor peak for each donor. For oxidized VLDL phospholipids, the area of the major peak reduced for three donors, possibly due to phospholipid decomposition. For glycated VLDL phospholipids, the peak mobilities were more positive than native VLDL phospholipids for two donors, possibly due to phospholipid-linked advanced glycation end products (AGEs). Very interestingly, at absorbance 234 nm, the major peak of oxidized VLDL phospholipids was resolved as two peaks for each donor, possibly due to conjugated dienes formed upon oxidation. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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14 pages, 494 KiB

Open AccessArticle

Lysophosphatidylcholine Acyltransferase 3 Is the Key Enzyme for Incorporating Arachidonic Acid into Glycerophospholipids during Adipocyte Differentiation

by Miki Eto, Hideo Shindou, Andreas Koeberle, Takeshi Harayama, Keisuke Yanagida and Takao Shimizu

Int. J. Mol. Sci. 2012, 13(12), 16267-16280; https://doi.org/10.3390/ijms131216267 - 3 Dec 2012

Cited by 36 | Viewed by 9397

Abstract

Cellular membranes contain glycerophospholipids, which have important structural and functional roles in cells. Glycerophospholipids are first formed in the de novo pathway (Kennedy pathway) and are matured in the remodeling pathway (Lands’ cycle). Recently, lysophospholipid acyltransferases functioning in Lands’ cycle were identified and [...] Read more.

Cellular membranes contain glycerophospholipids, which have important structural and functional roles in cells. Glycerophospholipids are first formed in the de novo pathway (Kennedy pathway) and are matured in the remodeling pathway (Lands’ cycle). Recently, lysophospholipid acyltransferases functioning in Lands’ cycle were identified and characterized. Several enzymes involved in glycerophospholipid biosynthesis have been reported to have important roles in adipocytes. However, the role of Lands’ cycle in adipogenesis has not yet been reported. Using C3H10T1/2, a cell line capable of differentiating to adipocyte-like cells in vitro, changes of lysophospholipid acyltransferase activities were investigated. Lysophosphatidylcholine acyltransferase (LPCAT), lysophosphatidylethanolamine acyltransferase (LPEAT) and lysophosphatidylserine acyltransferase (LPSAT) activities were enhanced, especially with 18:2-CoA and 20:4-CoA as donors. Correspondingly, mRNA expression of LPCAT3, which possesses LPCAT, LPEAT and LPSAT activities with high specificity for 18:2- and 20:4-CoA, was upregulated during adipogenesis. Analysis of acyl-chain compositions of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS) showed a change in their profiles between preadipocytes and adipocytes, including an increase in the percentage of arachidonic acid-containing phospholipids. These changes are consistent with the activities of LPCAT3. Therefore, it is possible that enhanced phospholipid remodeling by LPCAT3 may be associated with adipocyte differentiation. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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25 pages, 676 KiB

Open AccessArticle

Phosphatidylethanol in Blood as a Marker of Chronic Alcohol Use: A Systematic Review and Meta-Analysis

by Guido Viel, Rafael Boscolo-Berto, Giovanni Cecchetto, Paolo Fais, Alessandro Nalesso and Santo Davide Ferrara

Int. J. Mol. Sci. 2012, 13(11), 14788-14812; https://doi.org/10.3390/ijms131114788 - 13 Nov 2012

Cited by 208 | Viewed by 17202

Abstract

The present paper aims at a systematic review of the current knowledge on phosphatidylethanol (PEth) in blood as a direct marker of chronic alcohol use and abuse. In March 2012, the search through “MeSH” and “free-text” protocols in the databases Medline/PubMed, SCOPUS, Web [...] Read more.

The present paper aims at a systematic review of the current knowledge on phosphatidylethanol (PEth) in blood as a direct marker of chronic alcohol use and abuse. In March 2012, the search through “MeSH” and “free-text” protocols in the databases Medline/PubMed, SCOPUS, Web of Science, and Ovid/Embase, combining the terms phosphatidylethanol and alcohol, provided 444 records, 58 of which fulfilled the inclusion criteria and were used to summarize the current evidence on the formation, distribution and degradation of PEth in human blood: (1), the presence and distribution of different PEth molecular species (2), the most diffused analytical methods devoted to PEth identification and quantization (3), the clinical efficiency of total PEth quantification as a marker of chronic excessive drinking (4), and the potential utility of this marker for identifying binge drinking behaviors (5). Twelve papers were included in the meta-analysis and the mean (M) and 95% confidence interval (CI) of total PEth concentrations in social drinkers (DAI ≤ 60 g/die; M = 0.288 µM; CI 0.208–0.367 µM) and heavy drinkers (DAI > 60 g/die; M = 3.897 µM; CI 2.404–5.391 µM) were calculated. The present analysis demonstrates a good clinical efficiency of PEth for detecting chronic heavy drinking. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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Review

Jump to: Research

22 pages, 935 KiB

Open AccessReview

Dietary Polyunsaturated Fatty Acids and Inflammation: The Role of Phospholipid Biosynthesis

by William Raphael and Lorraine M. Sordillo

Int. J. Mol. Sci. 2013, 14(10), 21167-21188; https://doi.org/10.3390/ijms141021167 - 22 Oct 2013

Cited by 137 | Viewed by 16863

Abstract

The composition of fatty acids in the diets of both human and domestic animal species can regulate inflammation through the biosynthesis of potent lipid mediators. The substrates for lipid mediator biosynthesis are derived primarily from membrane phospholipids and reflect dietary fatty acid intake. [...] Read more.

The composition of fatty acids in the diets of both human and domestic animal species can regulate inflammation through the biosynthesis of potent lipid mediators. The substrates for lipid mediator biosynthesis are derived primarily from membrane phospholipids and reflect dietary fatty acid intake. Inflammation can be exacerbated with intake of certain dietary fatty acids, such as some ω-6 polyunsaturated fatty acids (PUFA), and subsequent incorporation into membrane phospholipids. Inflammation, however, can be resolved with ingestion of other fatty acids, such as ω-3 PUFA. The influence of dietary PUFA on phospholipid composition is influenced by factors that control phospholipid biosynthesis within cellular membranes, such as preferential incorporation of some fatty acids, competition between newly ingested PUFA and fatty acids released from stores such as adipose, and the impacts of carbohydrate metabolism and physiological state. The objective of this review is to explain these factors as potential obstacles to manipulating PUFA composition of tissue phospholipids by specific dietary fatty acids. A better understanding of the factors that influence how dietary fatty acids can be incorporated into phospholipids may lead to nutritional intervention strategies that optimize health. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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28 pages, 1460 KiB

Open AccessReview

Phospholipids at the Interface: Current Trends and Challenges

by Roman Pichot, Richard L. Watson and Ian T. Norton

Int. J. Mol. Sci. 2013, 14(6), 11767-11794; https://doi.org/10.3390/ijms140611767 - 3 Jun 2013

Cited by 201 | Viewed by 15848

Abstract

Phospholipids are one of the major structural elements of biological membranes. Due to their amphiphilic character, they can adopt various molecular assemblies when dispersed in water, such as bilayer vesicles or micelles, which give them unique interfacial properties and render them very attractive [...] Read more.

Phospholipids are one of the major structural elements of biological membranes. Due to their amphiphilic character, they can adopt various molecular assemblies when dispersed in water, such as bilayer vesicles or micelles, which give them unique interfacial properties and render them very attractive in terms of foam or emulsion stabilization. This article aims at reviewing the properties of phospholipids at the air/water and oil/water interfaces, as well as the recent advances in using these natural components as stabilizers, alone or in combination with other compounds such as proteins. A discussion regarding the challenges and opportunities offered by phospholipids-stabilized structure concludes the review. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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21 pages, 773 KiB

Open AccessReview

Crosstalk between DnaA Protein, the Initiator of Escherichia coli Chromosomal Replication, and Acidic Phospholipids Present in Bacterial Membranes

by Rahul Saxena, Nicholas Fingland, Digvijay Patil, Anjali K. Sharma and Elliott Crooke

Int. J. Mol. Sci. 2013, 14(4), 8517-8537; https://doi.org/10.3390/ijms14048517 - 17 Apr 2013

Cited by 45 | Viewed by 10415

Abstract

Anionic (i.e., acidic) phospholipids such as phosphotidylglycerol (PG) and cardiolipin (CL), participate in several cellular functions. Here we review intriguing in vitro and in vivo evidence that suggest emergent roles for acidic phospholipids in regulating DnaA protein-mediated initiation of Escherichia coli [...] Read more.

Anionic (i.e., acidic) phospholipids such as phosphotidylglycerol (PG) and cardiolipin (CL), participate in several cellular functions. Here we review intriguing in vitro and in vivo evidence that suggest emergent roles for acidic phospholipids in regulating DnaA protein-mediated initiation of Escherichia coli chromosomal replication. In vitro acidic phospholipids in a fluid bilayer promote the conversion of inactive ADP-DnaA to replicatively proficient ATP-DnaA, yet both PG and CL also can inhibit the DNA-binding activity of DnaA protein. We discuss how cellular acidic phospholipids may positively and negatively influence the initiation activity of DnaA protein to help assure chromosomal replication occurs once, but only once, per cell-cycle. Fluorescence microscopy has revealed that PG and CL exist in domains located at the cell poles and mid-cell, and several studies link membrane curvature with sub-cellular localization of various integral and peripheral membrane proteins. E. coli DnaA itself is found at the cell membrane and forms helical structures along the longitudinal axis of the cell. We propose that there is cross-talk between acidic phospholipids in the bacterial membrane and DnaA protein as a means to help control the spatial and temporal regulation of chromosomal replication in bacteria. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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16 pages, 1730 KiB

Open AccessReview

Phospholipid Membrane Protection by Sugar Molecules during Dehydration—Insights into Molecular Mechanisms Using Scattering Techniques

by Christopher J. Garvey, Thomas Lenné, Karen L. Koster, Ben Kent and Gary Bryant

Int. J. Mol. Sci. 2013, 14(4), 8148-8163; https://doi.org/10.3390/ijms14048148 - 12 Apr 2013

Cited by 31 | Viewed by 9316

Abstract

Scattering techniques have played a key role in our understanding of the structure and function of phospholipid membranes. These techniques have been applied widely to study how different molecules (e.g., cholesterol) can affect phospholipid membrane structure. However, there has been much less attention [...] Read more.

Scattering techniques have played a key role in our understanding of the structure and function of phospholipid membranes. These techniques have been applied widely to study how different molecules (e.g., cholesterol) can affect phospholipid membrane structure. However, there has been much less attention paid to the effects of molecules that remain in the aqueous phase. One important example is the role played by small solutes, particularly sugars, in protecting phospholipid membranes during drying or slow freezing. In this paper, we present new results and a general methodology, which illustrate how contrast variation small angle neutron scattering (SANS) and synchrotron-based X-ray scattering (small angle (SAXS) and wide angle (WAXS)) can be used to quantitatively understand the interactions between solutes and phospholipids. Specifically, we show the assignment of lipid phases with synchrotron SAXS and explain how SANS reveals the exclusion of sugars from the aqueous region in the particular example of hexagonal II phases formed by phospholipids. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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26 pages, 1464 KiB

Open AccessReview

P4 ATPases: Flippases in Health and Disease

by Vincent A. Van der Mark, Ronald P.J. Oude Elferink and Coen C. Paulusma

Int. J. Mol. Sci. 2013, 14(4), 7897-7922; https://doi.org/10.3390/ijms14047897 - 11 Apr 2013

Cited by 102 | Viewed by 13923

Abstract

P4 ATPases catalyze the translocation of phospholipids from the exoplasmic to the cytosolic leaflet of biological membranes, a process termed “lipid flipping”. Accumulating evidence obtained in lower eukaryotes points to an important role for P4 ATPases in vesicular protein trafficking. The human genome [...] Read more.

P4 ATPases catalyze the translocation of phospholipids from the exoplasmic to the cytosolic leaflet of biological membranes, a process termed “lipid flipping”. Accumulating evidence obtained in lower eukaryotes points to an important role for P4 ATPases in vesicular protein trafficking. The human genome encodes fourteen P4 ATPases (fifteen in mouse) of which the cellular and physiological functions are slowly emerging. Thus far, deficiencies of at least two P4 ATPases, ATP8B1 and ATP8A2, are the cause of severe human disease. However, various mouse models and in vitro studies are contributing to our understanding of the cellular and physiological functions of P4-ATPases. This review summarizes current knowledge on the basic function of these phospholipid translocating proteins, their proposed action in intracellular vesicle transport and their physiological role. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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26 pages, 801 KiB

Open AccessReview

Sphingomyelin in High-Density Lipoproteins: Structural Role and Biological Function

by Roberto Martínez-Beamonte, Jose M. Lou-Bonafonte, María V. Martínez-Gracia and Jesús Osada

Int. J. Mol. Sci. 2013, 14(4), 7716-7741; https://doi.org/10.3390/ijms14047716 - 9 Apr 2013

Cited by 62 | Viewed by 12582

Abstract

High-density lipoprotein (HDL) levels are an inverse risk factor for cardiovascular diseases, and sphingomyelin (SM) is the second most abundant phospholipid component and the major sphingolipid in HDL. Considering the marked presence of SM, the present review has focused on the current knowledge [...] Read more.

High-density lipoprotein (HDL) levels are an inverse risk factor for cardiovascular diseases, and sphingomyelin (SM) is the second most abundant phospholipid component and the major sphingolipid in HDL. Considering the marked presence of SM, the present review has focused on the current knowledge about this phospholipid by addressing its variable distribution among HDL lipoparticles, how they acquire this phospholipid, and the important role that SM plays in regulating their fluidity and cholesterol efflux from different cells. In addition, plasma enzymes involved in HDL metabolism such as lecithin–cholesterol acyltransferase or phospholipid transfer protein are inhibited by HDL SM content. Likewise, HDL SM levels are influenced by dietary maneuvers (source of protein or fat), drugs (statins or diuretics) and modified in diseases such as diabetes, renal failure or Niemann–Pick disease. Furthermore, increased levels of HDL SM have been shown to be an inverse risk factor for coronary heart disease. The complexity of SM species, described using new lipidomic methodologies, and their distribution in different HDL particles under many experimental conditions are promising avenues for further research in the future. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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47 pages, 1548 KiB

Open AccessReview

Annexin A2 Heterotetramer: Structure and Function

by Alamelu Bharadwaj, Moamen Bydoun, Ryan Holloway and David Waisman

Int. J. Mol. Sci. 2013, 14(3), 6259-6305; https://doi.org/10.3390/ijms14036259 - 19 Mar 2013

Cited by 250 | Viewed by 28733

Abstract

Annexin A2 is a pleiotropic calcium- and anionic phospholipid-binding protein that exists as a monomer and as a heterotetrameric complex with the plasminogen receptor protein, S100A10. Annexin A2 has been proposed to play a key role in many processes including exocytosis, endocytosis, membrane [...] Read more.

Annexin A2 is a pleiotropic calcium- and anionic phospholipid-binding protein that exists as a monomer and as a heterotetrameric complex with the plasminogen receptor protein, S100A10. Annexin A2 has been proposed to play a key role in many processes including exocytosis, endocytosis, membrane organization, ion channel conductance, and also to link F-actin cytoskeleton to the plasma membrane. Despite an impressive list of potential binding partners and regulatory activities, it was somewhat unexpected that the annexin A2-null mouse should show a relatively benign phenotype. Studies with the annexin A2-null mouse have suggested important functions for annexin A2 and the heterotetramer in fibrinolysis, in the regulation of the LDL receptor and in cellular redox regulation. However, the demonstration that depletion of annexin A2 causes the depletion of several other proteins including S100A10, fascin and affects the expression of at least sixty-one genes has confounded the reports of its function. In this review we will discuss the annexin A2 structure and function and its proposed physiological and pathological roles. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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17 pages, 621 KiB

Open AccessReview

The Lipid Transfer Protein StarD7: Structure, Function, and Regulation

by Jésica Flores-Martin, Viviana Rena, Sofía Angeletti, Graciela M. Panzetta-Dutari and Susana Genti-Raimondi

Int. J. Mol. Sci. 2013, 14(3), 6170-6186; https://doi.org/10.3390/ijms14036170 - 18 Mar 2013

Cited by 29 | Viewed by 10962

Abstract

The steroidogenic acute regulatory (StAR) protein-related lipid transfer (START) domain proteins constitute a family of evolutionarily conserved and widely expressed proteins that have been implicated in lipid transport, metabolism, and signaling. The 15 well-characterized mammalian START domain-containing proteins are grouped into six subfamilies. [...] Read more.

The steroidogenic acute regulatory (StAR) protein-related lipid transfer (START) domain proteins constitute a family of evolutionarily conserved and widely expressed proteins that have been implicated in lipid transport, metabolism, and signaling. The 15 well-characterized mammalian START domain-containing proteins are grouped into six subfamilies. The START domain containing 7 mRNA encodes StarD7, a member of the StarD2/phosphatidylcholine transfer protein (PCTP) subfamily, which was first identified as a gene overexpressed in a choriocarcinoma cell line. Recent studies show that the StarD7 protein facilitates the delivery of phosphatidylcholine to the mitochondria. This review summarizes the latest advances in StarD7 research, focusing on the structural and biochemical features, protein-lipid interactions, and mechanisms that regulate StarD7 expression. The implications of the role of StarD7 in cell proliferation, migration, and differentiation are also discussed. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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94 pages, 1156 KiB

Open AccessReview

Phospholipases of Mineralization Competent Cells and Matrix Vesicles: Roles in Physiological and Pathological Mineralizations

by Saida Mebarek, Abdelkarim Abousalham, David Magne, Le Duy Do, Joanna Bandorowicz-Pikula, Slawomir Pikula and René Buchet

Int. J. Mol. Sci. 2013, 14(3), 5036-5129; https://doi.org/10.3390/ijms14035036 - 1 Mar 2013

Cited by 56 | Viewed by 15862

Abstract

The present review aims to systematically and critically analyze the current knowledge on phospholipases and their role in physiological and pathological mineralization undertaken by mineralization competent cells. Cellular lipid metabolism plays an important role in biological mineralization. The physiological mechanisms of mineralization are [...] Read more.

The present review aims to systematically and critically analyze the current knowledge on phospholipases and their role in physiological and pathological mineralization undertaken by mineralization competent cells. Cellular lipid metabolism plays an important role in biological mineralization. The physiological mechanisms of mineralization are likely to take place in tissues other than in bones and teeth under specific pathological conditions. For instance, vascular calcification in arteries of patients with renal failure, diabetes mellitus or atherosclerosis recapitulates the mechanisms of bone formation. Osteoporosis—a bone resorbing disease—and rheumatoid arthritis originating from the inflammation in the synovium are also affected by cellular lipid metabolism. The focus is on the lipid metabolism due to the effects of dietary lipids on bone health. These and other phenomena indicate that phospholipases may participate in bone remodelling as evidenced by their expression in smooth muscle cells, in bone forming osteoblasts, chondrocytes and in bone resorbing osteoclasts. Among various enzymes involved, phospholipases A₁ or A₂, phospholipase C, phospholipase D, autotaxin and sphingomyelinase are engaged in membrane lipid remodelling during early stages of mineralization and cell maturation in mineralization-competent cells. Numerous experimental evidences suggested that phospholipases exert their action at various stages of mineralization by affecting intracellular signaling and cell differentiation. The lipid metabolites—such as arachidonic acid, lysophospholipids, and sphingosine-1-phosphate are involved in cell signaling and inflammation reactions. Phospholipases are also important members of the cellular machinery engaged in matrix vesicle (MV) biogenesis and exocytosis. They may favour mineral formation inside MVs, may catalyse MV membrane breakdown necessary for the release of mineral deposits into extracellular matrix (ECM), or participate in hydrolysis of ECM. The biological functions of phospholipases are discussed from the perspective of animal and cellular knockout models, as well as disease implications, development of potent inhibitors and therapeutic interventions. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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13 pages, 213 KiB

Open AccessReview

The Apolipoprotein M–Sphingosine-1-Phosphate Axis: Biological Relevance in Lipoprotein Metabolism, Lipid Disorders and Atherosclerosis

by Bas W. C. Arkensteijn, Jimmy F. P. Berbée, Patrick C. N. Rensen, Lars B. Nielsen and Christina Christoffersen

Int. J. Mol. Sci. 2013, 14(3), 4419-4431; https://doi.org/10.3390/ijms14034419 - 25 Feb 2013

Cited by 37 | Viewed by 9561

Abstract

Apolipoprotein M (apoM) is a plasma apolipoprotein that mainly associates with high-density lipoproteins. Hence, most studies on apoM so far have investigated its effect on and association with lipid metabolism and atherosclerosis. The insight into apoM biology recently took a major turn. ApoM [...] Read more.

Apolipoprotein M (apoM) is a plasma apolipoprotein that mainly associates with high-density lipoproteins. Hence, most studies on apoM so far have investigated its effect on and association with lipid metabolism and atherosclerosis. The insight into apoM biology recently took a major turn. ApoM was identified as a carrier of the bioactive lipid sphingosine-1-phosphate (S1P). S1P activates five different G-protein-coupled receptors, known as the S1P-receptors 1–5 and, hence, affects a wide range of biological processes, such as lymphocyte trafficking, angiogenesis, wound repair and even virus suppression and cancer. The ability of apoM to bind S1P is due to a lipophilic binding pocket within the lipocalin structure of the apoM molecule. Mice overexpressing apoM have increased plasma S1P concentrations, whereas apoM-deficient mice have decreased S1P levels. ApoM-S1P is able to activate the S1P-receptor-1, affecting the function of endothelial cells, and apoM-deficient mice display impaired endothelial permeability in the lung. This review will focus on the putative biological roles of the new apoM–S1P axis in relation to lipoprotein metabolism, lipid disorders and atherosclerosis. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

41 pages, 2247 KiB

Open AccessReview

Lipid Nanotechnology

by Samaneh Mashaghi, Tayebeh Jadidi, Gijsje Koenderink and Alireza Mashaghi

Int. J. Mol. Sci. 2013, 14(2), 4242-4282; https://doi.org/10.3390/ijms14024242 - 21 Feb 2013

Cited by 190 | Viewed by 42351

Abstract

Nanotechnology is a multidisciplinary field that covers a vast and diverse array of devices and machines derived from engineering, physics, materials science, chemistry and biology. These devices have found applications in biomedical sciences, such as targeted drug delivery, bio-imaging, sensing and diagnosis of [...] Read more.

Nanotechnology is a multidisciplinary field that covers a vast and diverse array of devices and machines derived from engineering, physics, materials science, chemistry and biology. These devices have found applications in biomedical sciences, such as targeted drug delivery, bio-imaging, sensing and diagnosis of pathologies at early stages. In these applications, nano-devices typically interface with the plasma membrane of cells. On the other hand, naturally occurring nanostructures in biology have been a source of inspiration for new nanotechnological designs and hybrid nanostructures made of biological and non-biological, organic and inorganic building blocks. Lipids, with their amphiphilicity, diversity of head and tail chemistry, and antifouling properties that block nonspecific binding to lipid-coated surfaces, provide a powerful toolbox for nanotechnology. This review discusses the progress in the emerging field of lipid nanotechnology. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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16 pages, 253 KiB

Open AccessReview

The Role of Lipid Domains in Bacterial Cell Processes

by Imrich Barák and Katarína Muchová

Int. J. Mol. Sci. 2013, 14(2), 4050-4065; https://doi.org/10.3390/ijms14024050 - 18 Feb 2013

Cited by 114 | Viewed by 13638

Abstract

Membranes are vital structures for cellular life forms. As thin, hydrophobic films, they provide a physical barrier separating the aqueous cytoplasm from the outside world or from the interiors of other cellular compartments. They maintain a selective permeability for the import and export [...] Read more.

Membranes are vital structures for cellular life forms. As thin, hydrophobic films, they provide a physical barrier separating the aqueous cytoplasm from the outside world or from the interiors of other cellular compartments. They maintain a selective permeability for the import and export of water-soluble compounds, enabling the living cell to maintain a stable chemical environment for biological processes. Cell membranes are primarily composed of two crucial substances, lipids and proteins. Bacterial membranes can sense environmental changes or communication signals from other cells and they support different cell processes, including cell division, differentiation, protein secretion and supplementary protein functions. The original fluid mosaic model of membrane structure has been recently revised because it has become apparent that domains of different lipid composition are present in both eukaryotic and prokaryotic cell membranes. In this review, we summarize different aspects of phospholipid domain formation in bacterial membranes, mainly in Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. We describe the role of these lipid domains in membrane dynamics and the localization of specific proteins and protein complexes in relation to the regulation of cellular function. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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39 pages, 1216 KiB

Open AccessReview

Protein-Phospholipid Interactions in Nonclassical Protein Secretion: Problem and Methods of Study

by Igor Prudovsky, Thallapuranam Krishnaswamy Suresh Kumar, Sarah Sterling and David Neivandt

Int. J. Mol. Sci. 2013, 14(2), 3734-3772; https://doi.org/10.3390/ijms14023734 - 8 Feb 2013

Cited by 25 | Viewed by 8589

Abstract

Extracellular proteins devoid of signal peptides use nonclassical secretion mechanisms for their export. These mechanisms are independent of the endoplasmic reticulum and Golgi. Some nonclassically released proteins, particularly fibroblast growth factors (FGF) 1 and 2, are exported as a result of their direct [...] Read more.

Extracellular proteins devoid of signal peptides use nonclassical secretion mechanisms for their export. These mechanisms are independent of the endoplasmic reticulum and Golgi. Some nonclassically released proteins, particularly fibroblast growth factors (FGF) 1 and 2, are exported as a result of their direct translocation through the cell membrane. This process requires specific interactions of released proteins with membrane phospholipids. In this review written by a cell biologist, a structural biologist and two membrane engineers, we discuss the following subjects: (i) Phenomenon of nonclassical protein release and its biological significance; (ii) Composition of the FGF1 multiprotein release complex (MRC); (iii) The relationship between FGF1 export and acidic phospholipid externalization; (iv) Interactions of FGF1 MRC components with acidic phospholipids; (v) Methods to study the transmembrane translocation of proteins; (vi) Membrane models to study nonclassical protein release. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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29 pages, 841 KiB

Open AccessReview

Non-Enzymatic Modification of Aminophospholipids by Carbonyl-Amine Reactions

by Alba Naudí, Mariona Jové, Victòria Ayala, Rosanna Cabré, Manuel Portero-Otín and Reinald Pamplona

Int. J. Mol. Sci. 2013, 14(2), 3285-3313; https://doi.org/10.3390/ijms14023285 - 5 Feb 2013

Cited by 34 | Viewed by 9618

Abstract

Non-enzymatic modification of aminophospholipids by lipid peroxidation-derived aldehydes and reducing sugars through carbonyl-amine reactions are thought to contribute to the age-related deterioration of cellular membranes and to the pathogenesis of diabetic complications. Much evidence demonstrates the modification of aminophospholipids by glycation, glycoxidation and [...] Read more.

Non-enzymatic modification of aminophospholipids by lipid peroxidation-derived aldehydes and reducing sugars through carbonyl-amine reactions are thought to contribute to the age-related deterioration of cellular membranes and to the pathogenesis of diabetic complications. Much evidence demonstrates the modification of aminophospholipids by glycation, glycoxidation and lipoxidation reactions. Therefore, a number of early and advanced Maillard reaction-lipid products have been detected and quantified in different biological membranes. These modifications may be accumulated during aging and diabetes, introducing changes in cell membrane physico-chemical and biological properties. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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24 pages, 229 KiB

Open AccessReview

Phospholipids in Milk Fat: Composition, Biological and Technological Significance, and Analytical Strategies

by Giovanna Contarini and Milena Povolo

Int. J. Mol. Sci. 2013, 14(2), 2808-2831; https://doi.org/10.3390/ijms14022808 - 29 Jan 2013

Cited by 259 | Viewed by 18828

Abstract

Glycerophospholipids and sphingolipids are quantitatively the most important phospholipids (PLs) in milk. They are located on the milk fat globule membrane (MFGM) and in other membranous material of the skim milk phase. They include principally phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine, while sphingomyelin is [...] Read more.

Glycerophospholipids and sphingolipids are quantitatively the most important phospholipids (PLs) in milk. They are located on the milk fat globule membrane (MFGM) and in other membranous material of the skim milk phase. They include principally phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine, while sphingomyelin is the dominant species of sphingolipids There is considerable evidence that PLs have beneficial health effects, such as regulation of the inflammatory reactions, chemopreventive and chemotherapeutic activity on some types of cancer, and inhibition of the cholesterol absorption. PLs show good emulsifying properties and can be used as a delivery system for liposoluble constituents. Due to the amphiphilic characteristics of these molecules, their extraction, separation and detection are critical points in the analytical approach. The extraction by using chloroform and methanol, followed by the determination by high pressure liquid chromatography (HPLC), coupled with evaporative light scattering (ELSD) or mass detector (MS), are the most applied procedures for the PL evaluation. More recently, nuclear magnetic resonance spectrometry (NMR) was also used, but despite it demonstrating high sensitivity, it requires more studies to obtain accurate results. This review is focused on milk fat phospholipids; their composition, biological activity, technological properties, and significance in the structure of milk fat. Different analytical methodologies are also discussed. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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32 pages, 2894 KiB

Open AccessReview

Annexin-Phospholipid Interactions. Functional Implications

by María Antonia Lizarbe, Juan I. Barrasa, Nieves Olmo, Francisco Gavilanes and Javier Turnay

Int. J. Mol. Sci. 2013, 14(2), 2652-2683; https://doi.org/10.3390/ijms14022652 - 28 Jan 2013

Cited by 193 | Viewed by 18204

Abstract

Annexins constitute an evolutionary conserved multigene protein superfamily characterized by their ability to interact with biological membranes in a calcium dependent manner. They are expressed by all living organisms with the exception of certain unicellular organisms. The vertebrate annexin core is composed of [...] Read more.

Annexins constitute an evolutionary conserved multigene protein superfamily characterized by their ability to interact with biological membranes in a calcium dependent manner. They are expressed by all living organisms with the exception of certain unicellular organisms. The vertebrate annexin core is composed of four (eight in annexin A6) homologous domains of around 70 amino acids, with the overall shape of a slightly bent ring surrounding a central hydrophilic pore. Calcium- and phospholipid-binding sites are located on the convex side while the N-terminus links domains I and IV on the concave side. The N-terminus region shows great variability in length and amino acid sequence and it greatly influences protein stability and specific functions of annexins. These proteins interact mainly with acidic phospholipids, such as phosphatidylserine, but differences are found regarding their affinity for lipids and calcium requirements for the interaction. Annexins are involved in a wide range of intra- and extracellular biological processes in vitro, most of them directly related with the conserved ability to bind to phospholipid bilayers: membrane trafficking, membrane-cytoskeleton anchorage, ion channel activity and regulation, as well as antiinflammatory and anticoagulant activities. However, the in vivo physiological functions of annexins are just beginning to be established. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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22 pages, 242 KiB

Open AccessReview

Regulation of Phosphatidylethanolamine Homeostasis — The Critical Role of CTP:Phosphoethanolamine Cytidylyltransferase (Pcyt2)

by Zvezdan Pavlovic and Marica Bakovic

Int. J. Mol. Sci. 2013, 14(2), 2529-2550; https://doi.org/10.3390/ijms14022529 - 25 Jan 2013

Cited by 78 | Viewed by 13787

Abstract

Phosphatidylethanolamine (PE) is the most abundant lipid on the protoplasmatic leaflet of cellular membranes. It has a pivotal role in cellular processes such as membrane fusion, cell cycle regulation, autophagy, and apoptosis. CTP:phosphoethanolamine cytidylyltransferase (Pcyt2) is the main regulatory enzyme in de novo [...] Read more.

Phosphatidylethanolamine (PE) is the most abundant lipid on the protoplasmatic leaflet of cellular membranes. It has a pivotal role in cellular processes such as membrane fusion, cell cycle regulation, autophagy, and apoptosis. CTP:phosphoethanolamine cytidylyltransferase (Pcyt2) is the main regulatory enzyme in de novo biosynthesis of PE from ethanolamine and diacylglycerol by the CDP-ethanolamine Kennedy pathway. The following is a summary of the current state of knowledge on Pcyt2 and how splicing and isoform specific differences could lead to variations in functional properties in this family of enzymes. Results from the most recent studies on Pcyt2 transcriptional regulation, promoter function, autophagy, and cell growth regulation are highlighted. Recent data obtained from Pcyt2 knockout mouse models is also presented, demonstrating the essentiality of this gene in embryonic development as well as the major physiological consequences of deletion of one Pcyt2 allele. Those include development of symptoms of the metabolic syndrome such as elevated lipogenesis and lipoprotein secretion, hypertriglyceridemia, liver steatosis, obesity, and insulin resistance. The objective of this review is to elucidate the nature of Pcyt2 regulation by linking its catalytic function with the regulation of lipid and energy homeostasis. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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21 pages, 1418 KiB

Open AccessReview

Thermotropic and Barotropic Phase Behavior of Phosphatidylcholine Bilayers

by Hitoshi Matsuki, Masaki Goto, Kaori Tada and Nobutake Tamai

Int. J. Mol. Sci. 2013, 14(2), 2282-2302; https://doi.org/10.3390/ijms14022282 - 24 Jan 2013

Cited by 55 | Viewed by 10222

Abstract

Bilayers formed by phospholipids are frequently used as model biological membranes in various life science studies. A characteristic feature of phospholipid bilayers is to undergo a structural change called a phase transition in response to environmental changes of their surroundings. In this review, [...] Read more.

Bilayers formed by phospholipids are frequently used as model biological membranes in various life science studies. A characteristic feature of phospholipid bilayers is to undergo a structural change called a phase transition in response to environmental changes of their surroundings. In this review, we focus our attention on phase transitions of some major phospholipids contained in biological membranes, phosphatidylcholines (PCs), depending on temperature and pressure. Bilayers of dipalmitoylphosphatidylcholine (DPPC), which is the most representative lipid in model membrane studies, will first be explained. Then, the bilayer phase behavior of various kinds of PCs with different molecular structures is revealed from the temperature–pressure phase diagrams, and the difference in phase stability among these PC bilayers is discussed in connection with the molecular structure of the PC molecules. Furthermore, the solvent effect on the phase behavior is also described briefly. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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19 pages, 639 KiB

Open AccessReview

Reconstitution of Membrane Proteins into Model Membranes: Seeking Better Ways to Retain Protein Activities

by Hsin-Hui Shen, Trevor Lithgow and Lisa Martin

Int. J. Mol. Sci. 2013, 14(1), 1589-1607; https://doi.org/10.3390/ijms14011589 - 14 Jan 2013

Cited by 96 | Viewed by 14277

Abstract

The function of any given biological membrane is determined largely by the specific set of integral membrane proteins embedded in it, and the peripheral membrane proteins attached to the membrane surface. The activity of these proteins, in turn, can be modulated by the [...] Read more.

The function of any given biological membrane is determined largely by the specific set of integral membrane proteins embedded in it, and the peripheral membrane proteins attached to the membrane surface. The activity of these proteins, in turn, can be modulated by the phospholipid composition of the membrane. The reconstitution of membrane proteins into a model membrane allows investigation of individual features and activities of a given cell membrane component. However, the activity of membrane proteins is often difficult to sustain following reconstitution, since the composition of the model phospholipid bilayer differs from that of the native cell membrane. This review will discuss the reconstitution of membrane protein activities in four different types of model membrane — monolayers, supported lipid bilayers, liposomes and nanodiscs, comparing their advantages in membrane protein reconstitution. Variation in the surrounding model environments for these four different types of membrane layer can affect the three-dimensional structure of reconstituted proteins and may possibly lead to loss of the proteins activity. We also discuss examples where the same membrane proteins have been successfully reconstituted into two or more model membrane systems with comparison of the observed activity in each system. Understanding of the behavioral changes for proteins in model membrane systems after membrane reconstitution is often a prerequisite to protein research. It is essential to find better solutions for retaining membrane protein activities for measurement and characterization in vitro. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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13 pages, 190 KiB

Open AccessReview

Phospholipids and Alzheimer’s Disease: Alterations, Mechanisms and Potential Biomarkers

by Marko Kosicek and Silva Hecimovic

Int. J. Mol. Sci. 2013, 14(1), 1310-1322; https://doi.org/10.3390/ijms14011310 - 10 Jan 2013

Cited by 171 | Viewed by 11787

Abstract

Brain is one of the richest organs in lipid content. Phospholipids (glycerophospholipids and sphingolipids) are important building blocks of cell membranes, which provide an optimal environment for protein interactions, trafficking and function. Because of that, alterations in their cellular levels could lead to [...] Read more.

Brain is one of the richest organs in lipid content. Phospholipids (glycerophospholipids and sphingolipids) are important building blocks of cell membranes, which provide an optimal environment for protein interactions, trafficking and function. Because of that, alterations in their cellular levels could lead to different pathogenic processes in the brain, such as in Alzheimer’s disease (AD), the most common type of dementia among older populations. There is increasing evidence that phospholipid changes occur during pathogenic processes in AD. It is known that lipids are tightly connected with metabolism of the Amyloid Precursor Protein (APP), which produces Amyloid-beta peptide (Aβ), the main component of senile plaques, which represent the main pathological hallmark of AD. However, the mechanism(s) of the lipid-effect on Aβ metabolism and AD pathogenesis is still not completely understood. This review summarizes the current knowledge on phospholipid changes occurring during normal aging and discusses phospholipid changes in the human brain associated with different stages of AD, as well changes in the cerebrospinal fluid and blood/plasma, which are interesting potential biomarkers for AD diagnosis and disease monitoring. At the end, we have discussed future perspectives of phospholipid changes as potential biomarkers and as targets for development of novel treatment strategies against AD. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

17 pages, 189 KiB

Open AccessReview

Dietary Docosahexaenoic Acid (22:6) Incorporates into Cardiolipin at the Expense of Linoleic Acid (18:2): Analysis and Potential Implications

by Colin H. Cortie and Paul L. Else

Int. J. Mol. Sci. 2012, 13(11), 15447-15463; https://doi.org/10.3390/ijms131115447 - 21 Nov 2012

Cited by 26 | Viewed by 9235

Abstract

Cardiolipin is a signature phospholipid of major functional significance in mitochondria. In heart mitochondria the fatty acid composition of cardiolipin is commonly viewed as highly regulated due to its high levels of linoleic acid (18:2n − 6) and the dominant presence of [...] Read more.

Cardiolipin is a signature phospholipid of major functional significance in mitochondria. In heart mitochondria the fatty acid composition of cardiolipin is commonly viewed as highly regulated due to its high levels of linoleic acid (18:2n − 6) and the dominant presence of a 4×18:2 molecular species. However, analysis of data from a comprehensive compilation of studies reporting changes in fatty acid composition of cardiolipin in heart and liver mitochondria in response to dietary fat shows that, in heart the accrual of 18:2 into cardiolipin conforms strongly to its dietary availability at up to 20% of total dietary fatty acid and thereafter is regulated. In liver, no dietary conformer trend is apparent for 18:2 with regulated lower levels across the dietary range for 18:2. When 18:2 and docosahexaenoic acid (22:6n − 3) are present in the same diet, 22:6 is incorporated into cardiolipin of heart and liver at the expense of 18:2 when 22:6 is up to ~20% and 10% of total dietary fatty acid respectively. Changes in fatty acid composition in response to dietary fat are also compared for the two other main mitochondrial phospholipids, phosphatidylcholine and phosphatidylethanolamine, and the potential consequences of replacement of 18:2 with 22:6 in cardiolipin are discussed. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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19 pages, 585 KiB

Open AccessReview

Marine Omega-3 Phospholipids: Metabolism and Biological Activities

by Lena Burri, Nils Hoem, Sebastiano Banni and Kjetil Berge

Int. J. Mol. Sci. 2012, 13(11), 15401-15419; https://doi.org/10.3390/ijms131115401 - 21 Nov 2012

Cited by 225 | Viewed by 24276

Abstract

The biological activities of omega-3 fatty acids (n-3 FAs) have been under extensive study for several decades. However, not much attention has been paid to differences of dietary forms, such as triglycerides (TGs) versus ethyl esters or phospholipids (PLs). New innovative marine raw [...] Read more.

The biological activities of omega-3 fatty acids (n-3 FAs) have been under extensive study for several decades. However, not much attention has been paid to differences of dietary forms, such as triglycerides (TGs) versus ethyl esters or phospholipids (PLs). New innovative marine raw materials, like krill and fish by-products, present n-3 FAs mainly in the PL form. With their increasing availability, new evidence has emerged on n-3 PL biological activities and differences to n-3 TGs. In this review, we describe the recently discovered nutritional properties of n-3 PLs on different parameters of metabolic syndrome and highlight their different metabolic bioavailability in comparison to other dietary forms of n-3 FAs. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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