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Mass Spectrometry Application in Biology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (20 March 2014) | Viewed by 106947

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Guest Editor
McWhorter School of Pharmacy, Samford University, Birmingham, AL, USA
Interests: bioanalytical chemistry; mass spectrometry; efficacy and safety of new oncology therapeutics; in-vitro metabolism

Special Issue Information

Dear Colleagues,

Mass spectrometry (MS) has become a vital tool for scientist in exploring how biological systems function and how therapeutic drug intervention (both small molecules and biologics) impact these systems. The application of mass spectrometry has advanced our knowledge in the biological sciences through the study of proteins and peptides in proteomics and as biomarkers, imaging via MALDI MS, and analysis of SNP’s in the genome to allow personalized medical treatment. This special edition of International Journal of Molecular Sciences: Mass Spectrometry in Biological Sciences will focus on the application of mass spectrometry to biological problems that focus on the advancement of medicine and curing diseases. Authors are invited to submit manuscripts that utilize mass spectrometry as a pivotal tool in research that involves understanding biological systems affected by disease states and the interaction of drug therapy on those systems.

Dr. Greg Gorman
Guest Editor

Manuscript Submission Information

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Keywords

  • mass spectrometry
  • biological systems
  • drug therapy
  • disease
  • proteins
  • peptides
  • nucleic acids
  • carbohydrates
  • proteomics
  • biomarkers

Published Papers (15 papers)

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1173 KiB  
Article
Radiosensitization of Human Leukemic HL-60 Cells by ATR Kinase Inhibitor (VE-821): Phosphoproteomic Analysis
by Barbora Šalovská, Ivo Fabrik, Kamila Ďurišová, Marek Link, Jiřina Vávrová, Martina Řezáčová and Aleš Tichý
Int. J. Mol. Sci. 2014, 15(7), 12007-12026; https://doi.org/10.3390/ijms150712007 - 7 Jul 2014
Cited by 21 | Viewed by 7879
Abstract
DNA damaging agents such as ionizing radiation or chemotherapy are frequently used in oncology. DNA damage response (DDR)—triggered by radiation-induced double strand breaks—is orchestrated mainly by three Phosphatidylinositol 3-kinase-related kinases (PIKKs): Ataxia teleangiectasia mutated (ATM), DNA-dependent protein kinase (DNA-PK) and ATM and Rad3-related [...] Read more.
DNA damaging agents such as ionizing radiation or chemotherapy are frequently used in oncology. DNA damage response (DDR)—triggered by radiation-induced double strand breaks—is orchestrated mainly by three Phosphatidylinositol 3-kinase-related kinases (PIKKs): Ataxia teleangiectasia mutated (ATM), DNA-dependent protein kinase (DNA-PK) and ATM and Rad3-related kinase (ATR). Their activation promotes cell-cycle arrest and facilitates DNA damage repair, resulting in radioresistance. Recently developed specific ATR inhibitor, VE-821 (3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide), has been reported to have a significant radio- and chemo-sensitizing effect delimited to cancer cells (largely p53-deficient) without affecting normal cells. In this study, we employed SILAC-based quantitative phosphoproteomics to describe the mechanism of the radiosensitizing effect of VE-821 in human promyelocytic leukemic cells HL-60 (p53-negative). Hydrophilic interaction liquid chromatography (HILIC)-prefractionation with TiO2-enrichment and nano-liquid chromatography—tandem mass spectrometry (LC-MS/MS) analysis revealed 9834 phosphorylation sites. Proteins with differentially up-/down-regulated phosphorylation were mostly localized in the nucleus and were involved in cellular processes such as DDR, all phases of the cell cycle, and cell division. Moreover, sequence motif analysis revealed significant changes in the activities of kinases involved in these processes. Taken together, our data indicates that ATR kinase has multiple roles in response to DNA damage throughout the cell cycle and that its inhibitor VE-821 is a potent radiosensitizing agent for p53-negative HL-60 cells. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
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821 KiB  
Article
Phosphorylation Stoichiometries of Human Eukaryotic Initiation Factors
by Armann Andaya, Nancy Villa, Weitao Jia, Christopher S. Fraser and Julie A. Leary
Int. J. Mol. Sci. 2014, 15(7), 11523-11538; https://doi.org/10.3390/ijms150711523 - 27 Jun 2014
Cited by 15 | Viewed by 6051
Abstract
Eukaryotic translation initiation factors are the principal molecular effectors regulating the process converting nucleic acid to functional protein. Commonly referred to as eIFs (eukaryotic initiation factors), this suite of proteins is comprised of at least 25 individual subunits that function in a coordinated, [...] Read more.
Eukaryotic translation initiation factors are the principal molecular effectors regulating the process converting nucleic acid to functional protein. Commonly referred to as eIFs (eukaryotic initiation factors), this suite of proteins is comprised of at least 25 individual subunits that function in a coordinated, regulated, manner during mRNA translation. Multiple facets of eIF regulation have yet to be elucidated; however, many of the necessary protein factors are phosphorylated. Herein, we have isolated, identified and quantified phosphosites from eIF2, eIF3, and eIF4G generated from log phase grown HeLa cell lysates. Our investigation is the first study to globally quantify eIF phosphosites and illustrates differences in abundance of phosphorylation between the residues of each factor. Thus, identification of those phosphosites that exhibit either high or low levels of phosphorylation under log phase growing conditions may aid researchers to concentrate their investigative efforts to specific phosphosites that potentially harbor important regulatory mechanisms germane to mRNA translation. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
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1626 KiB  
Article
Development of Laser Ionization Techniques for Evaluation of the Effect of Cancer Drugs Using Imaging Mass Spectrometry
by Hiroki Kannen, Hisanao Hazama, Yasufumi Kaneda, Tatsuya Fujino and Kunio Awazu
Int. J. Mol. Sci. 2014, 15(7), 11234-11244; https://doi.org/10.3390/ijms150711234 - 25 Jun 2014
Cited by 5 | Viewed by 5572
Abstract
Recently, combined therapy using chemotherapy and photodynamic therapy (PDT) has been proposed as a means of improving treatment outcomes. In order to evaluate the efficacy of combined therapy, it is necessary to determine the distribution of the anticancer drug and the photosensitizer. We [...] Read more.
Recently, combined therapy using chemotherapy and photodynamic therapy (PDT) has been proposed as a means of improving treatment outcomes. In order to evaluate the efficacy of combined therapy, it is necessary to determine the distribution of the anticancer drug and the photosensitizer. We investigated the use of imaging mass spectrometry (IMS) to simultaneously observe the distributions of an anticancer drug and photosensitizer administered to cancer cells. In particular, we sought to increase the sensitivity of detection of the anticancer drug docetaxel and the photosensitizer protoporphyrin IX (PpIX) by optimizing the ionization-assisting reagents. When we used a matrix consisting of equal weights of a zeolite (NaY5.6) and a conventional organic matrix (6-aza-2-thiothymine) in matrix-assisted laser desorption/ionization, the signal intensity of the sodium-adducted ion of docetaxel (administered at 100 μM) increased about 13-fold. Moreover, we detected docetaxel with the zeolite matrix using the droplet method, and detected PpIX by fluorescence and IMS with α-cyano-4-hydroxycinnamic acid (CHCA) using the spray method. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
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1605 KiB  
Article
Continuous Flow Atmospheric Pressure Laser Desorption/Ionization Using a 6–7-µm-Band Mid-Infrared Tunable Laser for Biomolecular Mass Spectrometry
by Ryuji Hiraguchi, Hisanao Hazama, Kenichirou Senoo, Yukinori Yahata, Katsuyoshi Masuda and Kunio Awazu
Int. J. Mol. Sci. 2014, 15(6), 10821-10834; https://doi.org/10.3390/ijms150610821 - 16 Jun 2014
Cited by 6 | Viewed by 6653
Abstract
A continuous flow atmospheric pressure laser desorption/ionization technique using a porous stainless steel probe and a 6–7-µm-band mid-infrared tunable laser was developed. This ion source is capable of direct ionization from a continuous flow with a high temporal stability. The 6–7-µm wavelength region [...] Read more.
A continuous flow atmospheric pressure laser desorption/ionization technique using a porous stainless steel probe and a 6–7-µm-band mid-infrared tunable laser was developed. This ion source is capable of direct ionization from a continuous flow with a high temporal stability. The 6–7-µm wavelength region corresponds to the characteristic absorption bands of various molecular vibration modes, including O–H, C=O, CH3 and C–N bonds. Consequently, many organic compounds and solvents, including water, have characteristic absorption peaks in this region. This ion source requires no additional matrix, and utilizes water or acetonitrile as the solvent matrix at several absorption peak wavelengths (6.05 and 7.27 µm, respectively). The distribution of multiply-charged peptide ions is extremely sensitive to the temperature of the heated capillary, which is the inlet of the mass spectrometer. This ionization technique has potential for the interface of liquid chromatography/mass spectrometry (LC/MS). Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
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552 KiB  
Article
Direct Analysis of hCGβcf Glycosylation in Normal and Aberrant Pregnancy by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry
by Ray K. Iles, Laurence A. Cole and Stephen A. Butler
Int. J. Mol. Sci. 2014, 15(6), 10067-10082; https://doi.org/10.3390/ijms150610067 - 5 Jun 2014
Cited by 11 | Viewed by 6500
Abstract
The analysis of human chorionic gonadotropin (hCG) in clinical chemistry laboratories by specific immunoassay is well established. However, changes in glycosylation are not as easily assayed and yet alterations in hCG glycosylation is associated with abnormal pregnancy. hCGβ-core fragment (hCGβcf) was isolated from [...] Read more.
The analysis of human chorionic gonadotropin (hCG) in clinical chemistry laboratories by specific immunoassay is well established. However, changes in glycosylation are not as easily assayed and yet alterations in hCG glycosylation is associated with abnormal pregnancy. hCGβ-core fragment (hCGβcf) was isolated from the urine of women, pregnant with normal, molar and hyperemesis gravidarum pregnancies. Each sample was subjected to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) analysis following dithiothreitol (DTT) reduction and fingerprint spectra of peptide hCGβ 6–40 were analyzed. Samples were variably glycosylated, where most structures were small, core and largely mono-antennary. Larger single bi-antennary and mixtures of larger mono-antennary and bi-antennary moieties were also observed in some samples. Larger glycoforms were more abundant in the abnormal pregnancies and tri-antennary carbohydrate moieties were only observed in the samples from molar and hyperemesis gravidarum pregnancies. Given that such spectral profiling differences may be characteristic, development of small sample preparation for mass spectral analysis of hCG may lead to a simpler and faster approach to glycostructural analysis and potentially a novel clinical diagnostic test. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
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1090 KiB  
Article
Quantitative Proteomics to Characterize Specific Histone H2A Proteolysis in Chronic Lymphocytic Leukemia and the Myeloid THP-1 Cell Line
by Pieter Glibert, Liesbeth Vossaert, Katleen Van Steendam, Stijn Lambrecht, Filip Van Nieuwerburgh, Fritz Offner, Thomas Kipps, Maarten Dhaenens and Dieter Deforce
Int. J. Mol. Sci. 2014, 15(6), 9407-9421; https://doi.org/10.3390/ijms15069407 - 27 May 2014
Cited by 10 | Viewed by 6795
Abstract
Proteome studies on hematological malignancies contribute to the understanding of the disease mechanism and to the identification of new biomarker candidates. With the isobaric tag for relative and absolute quantitation (iTRAQ) method we analyzed the protein expression between B-cells of healthy people and [...] Read more.
Proteome studies on hematological malignancies contribute to the understanding of the disease mechanism and to the identification of new biomarker candidates. With the isobaric tag for relative and absolute quantitation (iTRAQ) method we analyzed the protein expression between B-cells of healthy people and chronic lymphocytic leukemia (CLL) B-cells. CLL is the most common lymphoid cancer of the blood and is characterized by a variable clinical course. By comparing samples of patients with an aggressive vs. indolent disease, we identified a limited list of differentially regulated proteins. The enhanced sensitivity attributed to the iTRAQ labels led to the discovery of a previously reported but still not clarified proteolytic product of histone H2A (cH2A) which we further investigated in light of the suggested functional properties of this modification. In the exploratory proteome study the Histone H2A peptide was up-regulated in CLL samples but a more specific and sensitive screening of a larger patient cohort indicated that cH2A is of myeloid origin. Our subsequent quantitative analysis led to a more profound characterization of the clipping in acute monocytic leukemia THP-1 cells subjected to induced differentiation. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
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1225 KiB  
Article
Access of Hydrogen-Radicals to the Peptide-Backbone as a Measure for Estimating the Flexibility of Proteins Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry
by Mitsuo Takayama, Keishiro Nagoshi, Ryunosuke Iimuro and Kazuma Inatomi
Int. J. Mol. Sci. 2014, 15(5), 8428-8442; https://doi.org/10.3390/ijms15058428 - 13 May 2014
Cited by 8 | Viewed by 7016
Abstract
A factor for estimating the flexibility of proteins is described that uses a cleavage method of “in-source decay (ISD)” coupled with matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). The MALDI-ISD spectra of bovine serum albumin (BSA), myoglobin and thioredoxin show discontinuous intense ion [...] Read more.
A factor for estimating the flexibility of proteins is described that uses a cleavage method of “in-source decay (ISD)” coupled with matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). The MALDI-ISD spectra of bovine serum albumin (BSA), myoglobin and thioredoxin show discontinuous intense ion peaks originating from one-side preferential cleavage at the N-Cα bond of Xxx-Asp, Xxx-Asn, Xxx-Cys and Gly-Xxx residues. Consistent with these observations, Asp, Asn and Gly residues are also identified by other flexibility measures such as B-factor, turn preference, protection and fluorescence decay factors, while Asp, Asn, Cys and Gly residues are identified by turn preference factor based on X-ray crystallography. The results suggest that protein molecules embedded in/on MALDI matrix crystals partly maintain α-helix and that the reason some of the residues are more susceptible to ISD (Asp, Asn, Cys and Gly) and others less so (Ile and Val) is because of accessibility of the peptide backbone to hydrogen-radicals from matrix molecules. The hydrogen-radical accessibility in MALDI-ISD could therefore be adopted as a factor for measuring protein flexibility. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
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915 KiB  
Article
Legionella dumoffii Utilizes Exogenous Choline for Phosphatidylcholine Synthesis
by Marta Palusinska-Szysz, Agnieszka Szuster-Ciesielska, Magdalena Kania, Monika Janczarek, Elżbieta Chmiel and Witold Danikiewicz
Int. J. Mol. Sci. 2014, 15(5), 8256-8279; https://doi.org/10.3390/ijms15058256 - 9 May 2014
Cited by 7 | Viewed by 6916
Abstract
Phosphatidycholine (PC) is the major membrane-forming phospholipid in eukaryotes but it has been found in only a limited number of prokaryotes. Bacteria synthesize PC via the phospholipid N-methylation pathway (Pmt) or via the phosphatidylcholine synthase pathway (Pcs) or both. Here, we demonstrated [...] Read more.
Phosphatidycholine (PC) is the major membrane-forming phospholipid in eukaryotes but it has been found in only a limited number of prokaryotes. Bacteria synthesize PC via the phospholipid N-methylation pathway (Pmt) or via the phosphatidylcholine synthase pathway (Pcs) or both. Here, we demonstrated that Legionella dumoffii has the ability to utilize exogenous choline for phosphatidylcholine (PC) synthesis when bacteria grow in the presence of choline. The Pcs seems to be a primary pathway for synthesis of this phospholipid in L. dumoffii. Structurally different PC species were distributed in the outer and inner membranes. As shown by the LC/ESI-MS analyses, PC15:0/15:0, PC16:0/15:0, and PC17:0/17:1 were identified in the outer membrane and PC14:0/16:0, PC16:0/17:1, and PC20:0/15:0 in the inner membrane. L. dumoffii pcsA gene encoding phosphatidylcholine synthase revealed the highest sequence identity to pcsA of L. bozemanae (82%) and L. longbeachae (81%) and lower identity to pcsA of L. drancourtii (78%) and L. pneumophila (71%). The level of TNF-α in THP1-differentiated cells induced by live and temperature-killed L. dumoffii cultured on a medium supplemented with choline was assessed. Live L. dumoffii bacteria cultured on the choline-supplemented medium induced TNF-α three-fold less efficiently than cells grown on the non-supplemented medium. There is an evident effect of PC modification, which impairs the macrophage inflammatory response. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
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927 KiB  
Article
Radiation-Induced Changes in Serum Lipidome of Head and Neck Cancer Patients
by Karol Jelonek, Monika Pietrowska, Malgorzata Ros, Adam Zagdanski, Agnieszka Suchwalko, Joanna Polanska, Michal Marczyk, Tomasz Rutkowski, Krzysztof Skladowski, Malcolm R. Clench and Piotr Widlak
Int. J. Mol. Sci. 2014, 15(4), 6609-6624; https://doi.org/10.3390/ijms15046609 - 17 Apr 2014
Cited by 31 | Viewed by 7799
Abstract
Cancer radiotherapy (RT) induces response of the whole patient’s body that could be detected at the blood level. We aimed to identify changes induced in serum lipidome during RT and characterize their association with doses and volumes of irradiated tissue. Sixty-six patients treated [...] Read more.
Cancer radiotherapy (RT) induces response of the whole patient’s body that could be detected at the blood level. We aimed to identify changes induced in serum lipidome during RT and characterize their association with doses and volumes of irradiated tissue. Sixty-six patients treated with conformal RT because of head and neck cancer were enrolled in the study. Blood samples were collected before, during and about one month after the end of RT. Lipid extracts were analyzed using MALDI-oa-ToF mass spectrometry in positive ionization mode. The major changes were observed when pre-treatment and within-treatment samples were compared. Levels of several identified phosphatidylcholines, including (PC34), (PC36) and (PC38) variants, and lysophosphatidylcholines, including (LPC16) and (LPC18) variants, were first significantly decreased and then increased in post-treatment samples. Intensities of changes were correlated with doses of radiation received by patients. Of note, such correlations were more frequent when low-to-medium doses of radiation delivered during conformal RT to large volumes of normal tissues were analyzed. Additionally, some radiation-induced changes in serum lipidome were associated with toxicity of the treatment. Obtained results indicated the involvement of choline-related signaling and potential biological importance of exposure to clinically low/medium doses of radiation in patient’s body response to radiation. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
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1164 KiB  
Article
MALDI Q-TOF CID MS for Diagnostic Ion Screening of Human Milk Oligosaccharide Samples
by Marko Jovanović, Richard Tyldesley-Worster, Gottfried Pohlentz and Jasna Peter-Katalinić
Int. J. Mol. Sci. 2014, 15(4), 6527-6543; https://doi.org/10.3390/ijms15046527 - 16 Apr 2014
Cited by 13 | Viewed by 8639
Abstract
Human milk oligosaccharides (HMO) represent the bioactive components of human milk, influencing the infant’s gastrointestinal microflora and immune system. Structurally, they represent a highly complex class of analyte, where the main core oligosaccharide structures are built from galactose and N-acetylglucosamine, linked by [...] Read more.
Human milk oligosaccharides (HMO) represent the bioactive components of human milk, influencing the infant’s gastrointestinal microflora and immune system. Structurally, they represent a highly complex class of analyte, where the main core oligosaccharide structures are built from galactose and N-acetylglucosamine, linked by 1-3 or 1-4 glycosidic linkages and potentially modified with fucose and sialic acid residues. The core structures can be linear or branched. Additional structural complexity in samples can be induced by endogenous exoglycosidase activity or chemical procedures during the sample preparation. Here, we show that using matrix-assisted laser desorption/ionization (MALDI) quadrupole-time-of-flight (Q-TOF) collision-induced dissociation (CID) as a fast screening method, diagnostic structural information about single oligosaccharide components present in a complex mixture can be obtained. According to sequencing data on 14 out of 22 parent ions detected in a single high molecular weight oligosaccharide chromatographic fraction, 20 different oligosaccharide structure types, corresponding to over 30 isomeric oligosaccharide structures and over 100 possible HMO isomers when biosynthetic linkage variations were taken into account, were postulated. For MS/MS data analysis, we used the de novo sequencing approach using diagnostic ion analysis on reduced oligosaccharides by following known biosynthetic rules. Using this approach, de novo characterization has been achieved also for the structures, which could not have been predicted. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
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201 KiB  
Article
Interleukin-6 Receptor rs7529229 T/C Polymorphism Is Associated with Left Main Coronary Artery Disease Phenotype in a Chinese Population
by Feng He, Xiao Teng, Haiyong Gu, Hanning Liu, Zhou Zhou, Yan Zhao, Shengshou Hu and Zhe Zheng
Int. J. Mol. Sci. 2014, 15(4), 5623-5633; https://doi.org/10.3390/ijms15045623 - 2 Apr 2014
Cited by 18 | Viewed by 6434
Abstract
Left main coronary artery disease (LMCAD) is a particular severe phenotype of coronary artery disease (CAD) and heritability. Interleukin (IL) may play important roles in the pathogenesis of CAD. Although several single nucleotide polymorphisms (SNPs) identified in IL related genes have been evaluated [...] Read more.
Left main coronary artery disease (LMCAD) is a particular severe phenotype of coronary artery disease (CAD) and heritability. Interleukin (IL) may play important roles in the pathogenesis of CAD. Although several single nucleotide polymorphisms (SNPs) identified in IL related genes have been evaluated for their roles in inflammatory diseases and CAD predisposition, the investigations between genetic variants and CAD phenotype are limited. We hypothesized that some of these gene SNPs may contribute to LMCAD phenotype susceptibility compared with more peripheral coronary artery disease (MPCAD). In a hospital-based case-only study, we studied IL-1A rs1800587 C/T, IL-1B rs16944 G/A, IL-6 rs1800796 C/G, IL-6R rs7529229 T/C, IL-8 rs4073 T/A, IL-10 rs1800872 A/C, and IL-10 rs1800896 A/G SNPs in 402 LMCAD patients and 804 MPCAD patients in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and ligation detection reaction (LDR) method. When the IL-6R rs7529229 TT homozygote genotype was used as the reference group, the CC or TC/CC genotypes were associated with the increased risk for LMCAD (CC vs. TT, adjusted odds ratio(OR) = 1.46, 95% confidence interval (CI) = 1.02–2.11, p = 0.042; CC + TC vs. TT, adjusted OR = 1.31, 95% CI = 1.02–1.69, p = 0.037). None of the other six SNPs achieved any significant differences between LMCAD and MPCAD. The present study suggests that IL-6R rs7529229 T/C functional SNP may contribute to the risk of LMCAD in a Chinese population. However, our results were limited. Validation by a larger study from a more diverse ethnic population is needed. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
884 KiB  
Article
Investigation into Variation of Endogenous Metabolites in Bone Marrow Cells and Plasma in C3H/He Mice Exposed to Benzene
by Rongli Sun, Juan Zhang, Lihong Yin and Yuepu Pu
Int. J. Mol. Sci. 2014, 15(3), 4994-5010; https://doi.org/10.3390/ijms15034994 - 20 Mar 2014
Cited by 27 | Viewed by 6588
Abstract
Benzene is identified as a carcinogen. Continued exposure of benzene may eventually lead to damage to the bone marrow, accompanied by pancytopenia, aplastic anemia or leukemia. This paper explores the variations of endogenous metabolites to provide possible clues for the molecular mechanism of [...] Read more.
Benzene is identified as a carcinogen. Continued exposure of benzene may eventually lead to damage to the bone marrow, accompanied by pancytopenia, aplastic anemia or leukemia. This paper explores the variations of endogenous metabolites to provide possible clues for the molecular mechanism of benzene-induced hematotoxicity. Liquid chromatography coupled with time of flight-mass spectrometry (LC-TOF-MS) and principal component analysis (PCA) was applied to investigate the variation of endogenous metabolites in bone marrow cells and plasma of male C3H/He mice. The mice were injected subcutaneously with benzene (0, 300, 600 mg/day) once daily for seven days. The body weights, relative organ weights, blood parameters and bone marrow smears were also analyzed. The results indicated that benzene caused disturbances in the metabolism of oxidation of fatty acids and essential amino acids (lysine, phenylalanine and tyrosine) in bone marrow cells. Moreover, fatty acid oxidation was also disturbed in plasma and thus might be a common disturbed metabolic pathway induced by benzene in multiple organs. This study aims to investigate the underlying molecular mechanisms involved in benzene hematotoxicity, especially in bone marrow cells. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
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751 KiB  
Article
Phosphosite Mapping of HIP-55 Protein in Mammalian Cells
by Ning Liu, Ningning Sun, Xiang Gao and Zijian Li
Int. J. Mol. Sci. 2014, 15(3), 4903-4914; https://doi.org/10.3390/ijms15034903 - 19 Mar 2014
Cited by 5 | Viewed by 6350
Abstract
In the present study, hematopoietic progenitor kinase 1 (HPK1)-interacting protein of 55 kDa (HIP-55) protein was over-expressed in HEK293 cells, which was genetically attached with 6x His tag. The protein was purified by nickel-charged resin and was then subjected to [...] Read more.
In the present study, hematopoietic progenitor kinase 1 (HPK1)-interacting protein of 55 kDa (HIP-55) protein was over-expressed in HEK293 cells, which was genetically attached with 6x His tag. The protein was purified by nickel-charged resin and was then subjected to tryptic digestion. The phosphorylated peptides within the HIP-55 protein were enriched by TiO2 affinity chromatography, followed by mass spectrometry analysis. Fourteen phosphorylation sites along the primary structure of HIP-55 protein were identified, most of which had not been previously reported. Our results indicate that bio-mass spectrometry coupled with manual interpretation can be used to successfully identify the phosphorylation modification in HIP-55 protein in HEK293 cells. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
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596 KiB  
Communication
Mass Spectrometry Analysis Coupled with de novo Sequencing Reveals Amino Acid Substitutions in Nucleocapsid Protein from Influenza A Virus
by Zijian Li, Wanchun Sun, Donglin Wu, Xiang Gao, Ningning Sun and Ning Liu
Int. J. Mol. Sci. 2014, 15(2), 2465-2474; https://doi.org/10.3390/ijms15022465 - 11 Feb 2014
Cited by 8 | Viewed by 9582
Abstract
Amino acid substitutions in influenza A virus are the main reasons for both antigenic shift and virulence change, which result from non-synonymous mutations in the viral genome. Nucleocapsid protein (NP), one of the major structural proteins of influenza virus, is responsible for regulation [...] Read more.
Amino acid substitutions in influenza A virus are the main reasons for both antigenic shift and virulence change, which result from non-synonymous mutations in the viral genome. Nucleocapsid protein (NP), one of the major structural proteins of influenza virus, is responsible for regulation of viral RNA synthesis and replication. In this report we used LC-MS/MS to analyze tryptic digestion of nucleocapsid protein of influenza virus (A/Puerto Rico/8/1934 H1N1), which was isolated and purified by SDS poly-acrylamide gel electrophoresis. Thus, LC-MS/MS analyses, coupled with manual de novo sequencing, allowed the determination of three substituted amino acid residues R452K, T423A and N430T in two tryptic peptides. The obtained results provided experimental evidence that amino acid substitutions resulted from non-synonymous gene mutations could be directly characterized by mass spectrometry in proteins of RNA viruses such as influenza A virus. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
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Review

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481 KiB  
Review
Recent Advances in Bacteria Identification by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Using Nanomaterials as Affinity Probes
by Tai-Chia Chiu
Int. J. Mol. Sci. 2014, 15(5), 7266-7280; https://doi.org/10.3390/ijms15057266 - 28 Apr 2014
Cited by 17 | Viewed by 6733
Abstract
Identifying trace amounts of bacteria rapidly, accurately, selectively, and with high sensitivity is important to ensuring the safety of food and diagnosing infectious bacterial diseases. Microbial diseases constitute the major cause of death in many developing and developed countries of the world. The [...] Read more.
Identifying trace amounts of bacteria rapidly, accurately, selectively, and with high sensitivity is important to ensuring the safety of food and diagnosing infectious bacterial diseases. Microbial diseases constitute the major cause of death in many developing and developed countries of the world. The early detection of pathogenic bacteria is crucial in preventing, treating, and containing the spread of infections, and there is an urgent requirement for sensitive, specific, and accurate diagnostic tests. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is an extremely selective and sensitive analytical tool that can be used to characterize different species of pathogenic bacteria. Various functionalized or unmodified nanomaterials can be used as affinity probes to capture and concentrate microorganisms. Recent developments in bacterial detection using nanomaterials-assisted MALDI-MS approaches are highlighted in this article. A comprehensive table listing MALDI-MS approaches for identifying pathogenic bacteria, categorized by the nanomaterials used, is provided. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology)
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