Document Detail

Mass-spectrometric characterization of phospholipids and their primary peroxidation products in rat cortical neurons during staurosporine-induced apoptosis.
MedLine Citation:
PMID:  19014376     Owner:  NLM     Status:  MEDLINE    
The molecular diversity of phospholipids is essential for their structural and signaling functions in cell membranes. In the current work, we present, the results of mass spectrometric characterization of individual molecular species in major classes of phospholipids -- phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), phosphatidylserine (PtdSer), phosphatidylinositol (PtdIns), sphingomyelin (CerPCho), and cardiolipin (Ptd(2)Gro) -- and their oxidation products during apoptosis induced in neurons by staurosporine (STS). The diversity of molecular species of phospholipids in rat cortical neurons followed the order Ptd(2)Gro > PtdEtn >> PtdCho >> PtdSer > PtdIns > CerPCho. The number of polyunsaturated oxidizable species decreased in the order Ptd(2)Gro >> PtdEtn > PtdCho > PtdSer > PtdIns > CerPCho. Thus a relatively minor class of phospholipids, Ptd(2)Gro, was represented in cortical neurons by the greatest variety of both total and peroxidizable molecular species. Quantitative fluorescence HPLC analysis employed to assess the oxidation of different classes of phospholipids in neuronal cells during intrinsic apoptosis induced by STS revealed that three anionic phospholipids -- Ptd(2)Gro >> PtdSer > PtdIns -- underwent robust oxidation. No significant oxidation in the most dominant phospholipid classes -- PtdCho and PtdEtn -- was detected. MS-studies revealed the presence of hydroxy-, hydroperoxy- as well as hydroxy-/hydroperoxy-species of Ptd(2)Gro, PtdSer, and PtdIns. Experiments in model systems where total cortex Ptd(2)Gro and PtdSer fractions were incubated in the presence of cytochrome c (cyt c) and H(2)O(2), confirmed that molecular identities of the products formed were similar to the ones generated during STS-induced neuronal apoptosis. The temporal sequence of biomarkers of STS-induced apoptosis and phospholipid peroxidation combined with recently demonstrated redox catalytic properties of cyt c realized through its interactions with Ptd(2)Gro and PtdSer suggest that cyt c acts as a catalyst of selective peroxidation of anionic phospholipids yielding Ptd(2)Gro and PtdSer peroxidation products. These oxidation products participate in mitochondrial membrane permeability transition and in PtdSer externalization leading to recognition and uptake of apoptotic cells by professional phagocytes.
Vladimir A Tyurin; Yulia Y Tyurina; Weihong Feng; Alexandra Mnuskin; Jianfei Jiang; Minke Tang; Xiaojing Zhang; Qing Zhao; Patrick M Kochanek; Robert S B Clark; Hülya Bayir; Valerian E Kagan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-11-06
Journal Detail:
Title:  Journal of neurochemistry     Volume:  107     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-19     Completed Date:  2009-04-09     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1614-33     Citation Subset:  IM    
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MeSH Terms
Analysis of Variance
Apoptosis / drug effects*
Caspase 3 / metabolism
Cells, Cultured
Cerebral Cortex / cytology
Chromatography, High Pressure Liquid / methods
Cytochromes c / metabolism
Embryo, Mammalian
Enzyme Inhibitors / pharmacology*
Enzyme-Linked Immunosorbent Assay / methods
Lipid Peroxidation / drug effects*
Neurons / drug effects*,  physiology
Phospholipids / metabolism*
Rats, Sprague-Dawley
Spectrometry, Mass, Electrospray Ionization / methods
Staurosporine / pharmacology*
Time Factors
Grant Support
HD057587-01A2/HD/NICHD NIH HHS; HL70755/HL/NHLBI NIH HHS; NS061817/NS/NINDS NIH HHS; R01 HL070755/HL/NHLBI NIH HHS; R01 HL070755-05/HL/NHLBI NIH HHS; R03 TW007320/TW/FIC NIH HHS; R03 TW007320-02/TW/FIC NIH HHS; U19 AI068021/AI/NIAID NIH HHS; U19 AI068021-010002/AI/NIAID NIH HHS
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Phospholipids; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspase 3; H88EPA0A3N/Staurosporine

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