International Journal of Molecular Sciences

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9 pages, 263 KiB

Open AccessArticle

Mouse Plasminogen Has Oxidized Phosphatidylcholine Adducts That Are Not Metabolized by Lipoprotein-Associated Phospholipase A₂ under Basal Conditions

by Celina Edelstein, Ditta Pfaffinger, Ethan C. Reichert, Diana M. Stafforini and Angelo M. Scanu

Int. J. Mol. Sci. 2010, 11(12), 5339-5347; https://doi.org/10.3390/ijms11125339 - 22 Dec 2010

Cited by 3 | Viewed by 9802

Abstract

We previously showed that plasminogen (Plg) isolated from the plasma of normal human subjects contains 1–2 moles of oxidized phosphatidylcholine (oxPtdPC) adducts/mole of protein. Moreover, we suggested that these species are generated at the hepatic site and speculated that they may play a [...] Read more.

We previously showed that plasminogen (Plg) isolated from the plasma of normal human subjects contains 1–2 moles of oxidized phosphatidylcholine (oxPtdPC) adducts/mole of protein. Moreover, we suggested that these species are generated at the hepatic site and speculated that they may play a role in the reported cardiovascular pathogenicity of Plg. We aimed to determine whether mouse Plg also harbors linked oxPtdPCs and whether these molecules are metabolized by lipoprotein-associated phospholipase A₂/PAF acetylhydrolase (Lp-PLA₂/PAF-AH), an enzyme specific for hydrolysis of oxPtdPCs. We determined the total concentration of Plg in plasma samples from control (WT) and Lp-PLA₂-deficient (KO) mice, we isolated Plg, and assessed its content of oxPtdPCs by immunoblot analyses. We also evaluated whether human recombinant Lp-PLA₂ metabolized Plg-linked oxPtdPCs in vivo and in vitro. WT and KO mice expressed comparable levels (14.4–15.8 mg/dL) of plasma Plg, as determined by ELISA. We observed no differences in the content of oxPtdPC in Plg isolated from the two mouse strains and in parallel no changes in oxPtdPC content in mouse Plg following incubation with pure recombinant Lp-PLA₂. Plg from mouse plasma contains oxPtdPC adducts that are not affected by the action of Lp-PLA₂, suggesting that linkage to Plg protects oxPtdPCs from metabolism during their transport in the plasma. This modification may have important physio-pathological implications related to the function of Plg, oxPtdPCs, or both. Full article

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

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11 pages, 181 KiB

Open AccessArticle

Lysophosphatidic Acid Level and the Incidence of Silent Brain Infarction in Patients with Nonvalvular Atrial Fibrillation

by Zhen-Guang Li, Zhan-Cai Yu, Yong-Peng Yu, Wei-Ping Ju, Dao-Zhen Wang, Xia Zhan, Xi-Juan Wu and Li Zhou

Int. J. Mol. Sci. 2010, 11(10), 3988-3998; https://doi.org/10.3390/ijms11103988 - 19 Oct 2010

Cited by 19 | Viewed by 11657

Abstract

Lysophosphatidic acid (LPA), which is proposed to play an important role in normal physiological situations such as wound healing, vascular tone, vascular integrity and reproduction, may be involved in the etiology of some diseases such as atherosclerosis, cancer, obesity or myocardial infarction. Abnormal [...] Read more.

Lysophosphatidic acid (LPA), which is proposed to play an important role in normal physiological situations such as wound healing, vascular tone, vascular integrity and reproduction, may be involved in the etiology of some diseases such as atherosclerosis, cancer, obesity or myocardial infarction. Abnormal findings, including silent brain infarction (SBI), are frequently observed by magnetic resonance imaging (MRI) in patients with nonvalvular atrial fibrillation (NVAF). However, whether there is a relationship between LPA level and the prevalence of SBI has not been extensively studied. In the present study, the association between them was investigated. 235 patients with NVAF, 116 cases of SBI without NVAF and 120 cases of healthy volunteers (control group), who did not receive any antithrombotic therapy, were enrolled in this study. Plasma LPA levels in the NVAF with SBI group were significantly higher than that in the control group (p < 0.01), NVAF without SBI group (p < 0.01) and SBI without NVAF group (p < 0.01). The LPA levels are lower in the control group than in the NVAF without SBI and SBI without NVAF groups (p < 0.01), however, the latter two groups did not significantly differ from each other for LPA levels (p > 0.05) There were significant differences in the positive rate of platelet activation between each of the groups (p < 0.01). The positive rate of platelet activation was significantly higher in the NVAF with SBI group. We suggest that LPA might be a novel marker for estimation of the status of platelet activation and the risk factor for SBI onset in NVAF patients. We expected that plasma LPA levels could predict the occurrence of SBI in NVAF patients. Full article

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

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11 pages, 318 KiB

Open AccessArticle

The Effect of Exercise on the Skeletal Muscle Phospholipidome of Rats Fed a High-Fat Diet

by Todd W. Mitchell, Nigel Turner, Paul L. Else, Anthony J. Hulbert, John A. Hawley, Jong Sam Lee, Clinton R. Bruce and Stephen J. Blanksby

Int. J. Mol. Sci. 2010, 11(10), 3954-3964; https://doi.org/10.3390/ijms11103954 - 15 Oct 2010

Cited by 11 | Viewed by 13039

Abstract

The aim of this study was to examine the effect of endurance training on skeletal muscle phospholipid molecular species from high-fat fed rats. Twelve female Sprague-Dawley rats were fed a high-fat diet (78.1% energy). The rats were randomly divided into two groups, a [...] Read more.

The aim of this study was to examine the effect of endurance training on skeletal muscle phospholipid molecular species from high-fat fed rats. Twelve female Sprague-Dawley rats were fed a high-fat diet (78.1% energy). The rats were randomly divided into two groups, a sedentary control group and a trained group (125 min of treadmill running at 8 m/min, 4 days/wkfor 4 weeks). Forty-eight hours after their last training bout phospholipids were extracted from the red and white vastus lateralis and analyzed by electrospray-ionization mass spectrometry. Exercise training was associated with significant alterations in the relative abundance of a number of phospholipid molecular species. These changes were more prominent in red vastus lateralis than white vastus lateralis. The largest observed change was an increase of ~30% in the abundance of 1-palmitoyl-2-linoleoyl phosphatidylcholine ions in oxidative fibers. Reductions in the relative abundance of a number of phospholipids containing long-chain n-3 polyunsaturated fatty acids were also observed. These data suggest a possible reduction in phospholipid remodeling in the trained animals. This results in a decrease in the phospholipid n-3 to n-6 ratio that may in turn influence endurance capacity. Full article

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

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Review

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26 pages, 410 KiB

Open AccessReview

Nutritional Deficiencies and Phospholipid Metabolism

by María S. Gimenez, Liliana B. Oliveros and Nidia N. Gomez

Int. J. Mol. Sci. 2011, 12(4), 2408-2433; https://doi.org/10.3390/ijms12042408 - 6 Apr 2011

Cited by 45 | Viewed by 13210

Abstract

Phospholipids are important components of the cell membranes of all living species. They contribute to the physicochemical properties of the membrane and thus influence the conformation and function of membrane-bound proteins, such as receptors, ion channels, and transporters and also influence cell function [...] Read more.

Phospholipids are important components of the cell membranes of all living species. They contribute to the physicochemical properties of the membrane and thus influence the conformation and function of membrane-bound proteins, such as receptors, ion channels, and transporters and also influence cell function by serving as precursors for prostaglandins and other signaling molecules and modulating gene expression through the transcription activation. The components of the diet are determinant for cell functionality. In this review, the effects of macro and micronutrients deficiency on the quality, quantity and metabolism of different phospholipids and their distribution in cells of different organs is presented. Alterations in the amount of both saturated and polyunsaturated fatty acids, vitamins A, E and folate, and other micronutrients, such as zinc and magnesium, are discussed. In all cases we observe alterations in the pattern of phospholipids, the more affected ones being phosphatidylcholine, phosphatidylethanolamine and sphingomyelin. The deficiency of certain nutrients, such as essential fatty acids, fat-soluble vitamins and some metals may contribute to a variety of diseases that can be irreversible even after replacement with normal amount of the nutrients. Usually, the sequelae are more important when the deficiency is present at an early age. Full article

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

22 pages, 764 KiB

Open AccessReview

Integrated Lipidomics in the Secreted Phospholipase A₂ Biology

by Makoto Murakami, Hiroyasu Sato, Yoshitaka Taketomi and Kei Yamamoto

Int. J. Mol. Sci. 2011, 12(3), 1474-1495; https://doi.org/10.3390/ijms12031474 - 25 Feb 2011

Cited by 12 | Viewed by 8680

Abstract

Mammalian genomes encode genes for more than 30 phospholipase A₂s (PLA₂s) or related enzymes, which are subdivided into several subgroups based on their structures, catalytic mechanisms, localizations and evolutionary relationships. More than one third of the PLA₂ enzymes [...] Read more.

Mammalian genomes encode genes for more than 30 phospholipase A₂s (PLA₂s) or related enzymes, which are subdivided into several subgroups based on their structures, catalytic mechanisms, localizations and evolutionary relationships. More than one third of the PLA₂ enzymes belong to the secreted PLA₂ (sPLA₂) family, which consists of low-molecular-weight, Ca²⁺-requiring extracellular enzymes, with a His-Asp catalytic dyad. Individual sPLA₂ isoforms exhibit unique tissue and cellular localizations and enzymatic properties, suggesting their distinct pathophysiological roles. Recent studies using transgenic and knockout mice for several sPLA₂ isoforms, in combination with lipidomics approaches, have revealed their distinct contributions to various biological events. Herein, we will describe several examples of sPLA₂-mediated phospholipid metabolism in vivo, as revealed by integrated analysis of sPLA₂ transgenic/knockout mice and lipid mass spectrometry. Knowledge obtained from this approach greatly contributes to expanding our understanding of the sPLA₂ biology and pathophysiology. Full article

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

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25 pages, 421 KiB

Open AccessReview

Phospholipases A₁

by Gregory S. Richmond and Terry K. Smith

Int. J. Mol. Sci. 2011, 12(1), 588-612; https://doi.org/10.3390/ijms12010588 - 18 Jan 2011

Cited by 159 | Viewed by 16125

Abstract

Phospholipase A₁ (PLA₁) is an enzyme that hydrolyzes phospholipids and produces 2-acyl-lysophospholipids and fatty acids. This lipolytic activity is conserved in a wide range of organisms but is carried out by a diverse set of PLA₁ enzymes. Where their [...] Read more.

Phospholipase A₁ (PLA₁) is an enzyme that hydrolyzes phospholipids and produces 2-acyl-lysophospholipids and fatty acids. This lipolytic activity is conserved in a wide range of organisms but is carried out by a diverse set of PLA₁ enzymes. Where their function is known, PLA₁s have been shown to act as digestive enzymes, possess central roles in membrane maintenance and remodeling, or regulate important cellular mechanisms by the production of various lysophospholipid mediators, such as lysophosphatidylserine and lysophosphatidic acid, which in turn have multiple biological functions. Full article

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

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16 pages, 485 KiB

Open AccessReview

Lipid Based Therapy for Ulcerative Colitis—Modulation of Intestinal Mucus Membrane Phospholipids as a Tool to Influence Inflammation

by Hannah Schneider, Annika Braun, Joachim Füllekrug, Wolfgang Stremmel and Robert Ehehalt

Int. J. Mol. Sci. 2010, 11(10), 4149-4164; https://doi.org/10.3390/ijms11104149 - 25 Oct 2010

Cited by 65 | Viewed by 19316

Abstract

Ulcerative colitis (UC) is the result of an inappropriate colonic inflammatory response triggered by environmental and genetic factors. We have recently shown that mucus from UC patients has a decreased phosphatidylcholine (PC) content, while clinical trials revealed that therapeutic addition of PC to [...] Read more.

Ulcerative colitis (UC) is the result of an inappropriate colonic inflammatory response triggered by environmental and genetic factors. We have recently shown that mucus from UC patients has a decreased phosphatidylcholine (PC) content, while clinical trials revealed that therapeutic addition of PC to the colonic mucus alleviated the inflammatory activity. The mechanisms behind this are still unclear. We hypothesized that PC has at least two possible functions in the intestine: First, it establishes the surface hydrophobicity of the mucus and therefore protects the underlying tissue against intraluminal aggressors; recent experiments on surgical specimens revealed reduced surface tension and hydrophobicity in UC patients. Second, mucus phospholipids might also be integrated into the plasma membranes of enterocytes and thereby influence the signaling state of the mucosa. PC has been shown to inhibit TNF-α induced pro-inflammatory responses including: (1) assembly of plasma membrane actin; (2) activation of MAP kinases ERK and p38; and (3) activation of NF-κB and synthesis of pro-inflammatory gene products. Other phospholipids like phosphatidylethanolamine or sphingomyelin had no effect. PC also inhibited latex bead phagosome actin assembly, killing of M. tuberculosis in macrophages, and sphingosine-1-phosphate induced actin assembly in macrophages. Collectively, these results provide a molecular foundation that shows PC, firstly, as an anti-inflammatory, and secondly, as a surface hydrophobicity increasing compound with promising therapeutic potential in the treatment of inflammatory bowel disease. Full article

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

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