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Selective early cardiolipin peroxidation after traumatic brain injury: an oxidative lipidomics analysis
Author(s) -
Bayir Hülya,
Tyurin Vladimir A.,
Tyurina Yulia Y.,
Viner Rosa,
Ritov Vladimir,
Amoscato Andrew A.,
Zhao Qing,
Zhang Xiaojing J.,
JaneskoFeldman Keri L.,
Alexander Henry,
Basova Liana V.,
Clark Robert S. B.,
Kochanek Patrick M.,
Kagan Valerian E.
Publication year - 2007
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21168
Subject(s) - cardiolipin , lipid peroxidation , phosphatidylserine , phosphatidylethanolamine , chemistry , lipidomics , biochemistry , oxidative stress , phospholipid , glutathione , phosphatidylcholine , enzyme , membrane
Objective Enhanced lipid peroxidation is well established in traumatic brain injury. However, its molecular targets, identity of peroxidized phospholipid species, and their signaling role have not been deciphered. Methods Using controlled cortical impact as a model of traumatic brain injury, we employed a newly developed oxidative lipidomics approach to qualitatively and quantitatively characterize the lipid peroxidation response. Results Electrospray ionization and matrix‐assisted laser desorption/ionization mass spectrometry analysis of rat cortical mitochondrial/synaptosomal fractions demonstrated the presence of highly oxidizable molecular species containing C 22:6 fatty acid residues in all major classes of phospholipids. However, the pattern of phospholipid oxidation at 3 hours after injury displayed a nonrandom character independent of abundance of oxidizable species and included only one mitochondria‐specific phospholipid, cardiolipin (CL). This selective CL peroxidation was followed at 24 hours by peroxidation of other phospholipids, most prominently phosphatidylserine, but also phosphatidylcholine and phosphatidylethanolamine. CL oxidation preceded appearance of biomarkers of apoptosis (caspase‐3 activation, terminal deoxynucleotidyltransferase–mediated dUTP nick end labeling–positivity) and oxidative stress (loss of glutathione and ascorbate). Interpretation The temporal sequence combined with the recently demonstrated role of CL hydroperoxides (CL‐OOH) in in vitro models of apoptosis suggest that CL‐OOH may be both a key in vivo trigger of apoptotic cell death and a therapeutic target in experimental traumatic brain injury. Ann Neurol 2007