Selective Early Cardiolipin Peroxidation After Traumatic Brain Injury: An Oxidative Lipidomics Analysis

Details

• Personal Author:
  Alexander H ; Amoscato AA ; Basova LV ; Bayir H ; Clark RS ; Janesko-Feldman KL ; Kagan VE ; Kochanek PM ; Ritov V ; Tyurin VA ; Tyurina YY ; Viner R ; Zhang XJ ; Zhao Q
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Cardiovascular System Energy Metabolism Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Brain-damage Cardiac-function Cell-alteration Cell-biology Cell-damage Cell-differentiation Cell-function Cell-morphology Cellular-reactions Fatty-acids Metabolism Oxidation Physiology Qualitative-analysis Quantitative-analysis Traumatic-injuries

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• ISSN:
  0364-5134
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  154-169
• Volume:
  62
• Issue:
  2
• NIOSHTIC Number:
  nn:20032817
• Citation:
  Ann Neurol 2007 Aug; 62(2):154-169
• Contact Point Address:
  Dr Bayir, 3434 Fifth Avenue, Pittsburgh, PA 15213
• Federal Fiscal Year:
  2007
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Annals of Neurology
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:04baa15d6bc46e05080fe451580cadf04e7ea331076a4748601e85af90fbb0abd37cfc7131aa9abf87991578babb91001a3cb08f9758c87cd19956da777f3436
• Download URL:
  https://stacks.cdc.gov/view/cdc/186643/cdc_186643_DS1.pdf
• File Type:
  [PDF - 665.80 KB ]