New covalent modifications of phosphatidylethanolamine by alkanals: mass spectrometry based structural characterization and biological effects

被引:15
作者
Annibal, Andrea [1 ,2 ,3 ,4 ]
Schubert, Kristin [5 ]
Wagner, Ulf [5 ]
Hoffmann, Ralf [1 ,2 ,4 ]
Schiller, Juergen [2 ,3 ,4 ]
Fedorova, Maria [1 ,2 ]
机构
[1] Univ Leipzig, Fac Chem & Mineral, Inst Bioanalyt Chem, D-04109 Leipzig, Germany
[2] Univ Leipzig, Ctr Biotechnol & Biomed, D-04109 Leipzig, Germany
[3] Univ Leipzig, Fac Med, Inst Med Phys & Biophys, D-04109 Leipzig, Germany
[4] Univ Leipzig, LIFE Leipzig Res Ctr Civilizat Dis, D-04109 Leipzig, Germany
[5] Univ Leipzig, Dept Internal Med, Div Rheumatol, D-04109 Leipzig, Germany
来源
JOURNAL OF MASS SPECTROMETRY | 2014年 / 49卷 / 07期
关键词
lipid oxidation; MSn; high resolution MS; multiple reaction monitoring; alkanals; LIPID-PEROXIDATION PRODUCT; OXIDATIVE STRESS; PROTEIN CARBONYLATION; DAMAGE; IDENTIFICATION; MECHANISMS; MONOCYTES; QUANTIFICATION; DEGRADATION; DYSFUNCTION;
D O I
10.1002/jms.3373
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The pathophysiology of numerous human disorders, such as atherosclerosis, diabetes, obesity and Alzheimer's disease, is accompanied by increased production of reactive oxygen species (ROS). ROS can oxidatively damage nearly all biomolecules, including lipids, proteins and nucleic acids. In particular, (poly) unsaturated fatty acids within the phospholipid (PL) structure are easily oxidized by ROS to lipid peroxidation products (LPP) carrying reactive carbonyl groups. Carbonylated LPP are characterized by high in vivo toxicity due to their reactivity with nucleophilic substrates (Lys-, Cys-and His-residues in proteins or amino groups of phosphatidylethanolamines [PE]). Adducts of unsaturated LPP with PE amino groups have been reported before, whereas less is known about the reactivity of saturated alkanals - which are significantly increased in vivo under oxidative stress conditions - towards nucleophilic groups of PLs. Here, we present a study of new alkanal-dipalmitoyl-phosphatidylethanolamine (DPPE) adducts by MS-based approaches, using consecutive fragmentation (MSn) and multiple reaction monitoring techniques. At least eight different DPPE-hexanal adducts were identified, including Schiff base and amide adducts, six of which have not been reported before. The structures of these new compounds were determined by their fragmentation patterns using MSn experiments. The new PE-hexanal adducts contained dimeric and trimeric hexanal conjugates, including cyclic adducts. A new pyridine ring containing adduct of DPPE and hexanal was purified by HPLC, and its biological effects were investigated. Incubation of peripheral blood mononuclear cells and monocytes with modified DPPE did not result in increased production of TNF-alpha as one selected inflammation marker. However, incorporation of modified DPPE into 1,2-dipalmitoleoyl-sn-phosphatidylethanolamine multilamellar vesicles resulted in a negative shift of the transition temperature, indicating a possible role of alkanal-derived modifications in changes of membrane structure. Copyright (C) 2014 John Wiley & Sons, Ltd.
引用
收藏
页码:557 / 569
页数:13
相关论文
共 60 条
[1]  
Agarwal Rajiv, 2005, BMC Nephrol, V6, P13
[2]   BIOENERGETICS Proton fronts on membranes [J].
Agmon, Noam ;
Gutman, Menachem .
NATURE CHEMISTRY, 2011, 3 (11) :840-842
[3]   MEASURING LIPID OXIDATION VOLATILES IN MEATS [J].
AJUYAH, AO ;
FENTON, TW ;
HARDIN, RT ;
SIM, JS .
JOURNAL OF FOOD SCIENCE, 1993, 58 (02) :270-&
[4]   Reactive Oxygen Species in Health and Disease [J].
Alfadda, Assim A. ;
Sallam, Reem M. .
JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, 2012,
[5]   Membrane interaction and perturbation mechanisms induced by two cationic cell penetrating peptides with distinct charge distribution [J].
Alves, Isabel D. ;
Goasdoue, Nicole ;
Correia, Isabelle ;
Aubry, Soline ;
Galanth, Cecile ;
Sagan, Sandrine ;
Lavielle, Solange ;
Chassaing, Gerard .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2008, 1780 (7-8) :948-959
[6]   The oxidized form of cholesterol 3β-hydroxy-5-oxo-5,6-secocholestan-6-al induces structural and thermotropic changes in phospholipid membranes [J].
Bach, D. ;
Epand, R. F. ;
Epand, R. M. ;
Miller, I. R. ;
Wachtel, E. .
CHEMISTRY AND PHYSICS OF LIPIDS, 2009, 161 (02) :95-102
[7]   Oxidation of unsaturated phospholipids in membrane bilayer mixtures is accompanied by membrane fluidity changes [J].
Borst, JW ;
Visser, NV ;
Kouptsova, O ;
Visser, AJWG .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2000, 1487 (01) :61-73
[8]   Oxidative damage in human gingival fibroblasts exposed to cigarette smoke [J].
Colombo, Graziano ;
Dalle-Donne, Isabella ;
Orioli, Marica ;
Giustarini, Daniela ;
Rossi, Ranieri ;
Clerici, Marco ;
Regazzoni, Luca ;
Aldini, Giancarlo ;
Milzani, Aldo ;
Butterfield, D. Allan ;
Gagliano, Nicoletta .
FREE RADICAL BIOLOGY AND MEDICINE, 2012, 52 (09) :1584-1596
[9]   Protein carbonylation, cellular dysfunction, and disease progression [J].
Dalle-Donne, Isabella ;
Aldini, Giancarlo ;
Carini, Marina ;
Colombo, Roberto ;
Rossi, Ranieri ;
Milzani, Aldo .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2006, 10 (02) :389-406
[10]  
Dessi M., 2013, ISRN INFLAMM, V12