LC/MS characterization of rotenone induced cardiolipin oxidation in human lymphocytes: Implications for mitochondrial dysfunction associated with Parkinson's disease

Details

• Alternative Title:
  Mol Nutr Food Res
• Personal Author:
  Tyurina, Yulia Y. ; Winnica, Daniel E. ; Kapralova, Valentina I. ; Kapralov, Alexandr A. ; Tyurin, Vladimir A. ; Kagan, Valerian E.
• Description:
  Scope
  
  Rotenone is a toxicant believed to contribute to the development of Parkinson's disease.
  
  Methods and results
  
  Using human peripheral blood lymphocytes we demonstrated that exposure to rotenone resulted in disruption of electron transport accompanied by the production of reactive oxygen species, development of apoptosis and elevation of peroxidase activity of mitochondria. Employing LC/MS based lipidomics/oxidative lipidomics we characterized molecular species of cardiolipin (CL) and its oxidation/hydrolysis products formed early in apoptosis and associated with the rotenone-induced mitochondrial dysfunction.
  
  Conclusions
  
  The major oxidized CL species - tetra-linoleoyl-CL – underwent oxidation to yield epoxy-C18:2 and dihydroxy-C18:2 derivatives predominantly localized in sn-1 and sn-2 positions, respectively. In addition, accumulation of mono-lyso-CL species and oxygenated free C18:2 were detected in rotenone-treated lymphocytes. These oxidation/hydrolysis products may be useful for the development of new biomarkers of mitochondrial dysfunction.
  
  
• Subjects:
  Apoptosis Cardiolipins Cells, Cultured Chromatography, Liquid Humans Lymphocytes Lysophospholipids Mass Spectrometry Mitochondria Oxidation-Reduction Peroxidases Reactive Oxygen Species Rotenone

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• Keywords:
  Apoptosis Cardiolipin Peroxidation Lymphocytes Mitochondrial Dysfunction Parkinson's Disease Biomarkers
• Source:
  Mol Nutr Food Res. 57(8):1410-1422
• Pubmed ID:
  23650208
• Pubmed Central ID:
  PMC3810210
• Document Type:
  Journal Article
• Funding:
  R01 HL070755/HL/NHLBI NIH HHSUnited States/ ; R01 ES020693/ES/NIEHS NIH HHSUnited States/ ; R01 OH008282/OH/NIOSH CDC HHSUnited States/ ; U19 AI068021/AI/NIAID NIH HHSUnited States/ ; U19AIO68021/PHS HHSUnited States/ ; ES020693/ES/NIEHS NIH HHSUnited States/ ; OH008282/OH/NIOSH CDC HHSUnited States/ ; HL70755/HL/NHLBI NIH HHSUnited States/
• Volume:
  57
• Issue:
  8
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:c51f75fe711462aa2d523a9f565c68daff4d9e8dbdde2bdc09032179adf6f111
• Download URL:
  https://stacks.cdc.gov/view/cdc/29765/cdc_29765_DS1.pdf
• File Type:
  [PDF - 947.22 KB ]