LC/MS characterization of rotenone induced cardiolipin oxidation in human lymphocytes: implications for mitochondrial dysfunction associated with Parkinson's disease.
Tyurina YY; Winnica DE; Kapralova VI; Kapralov AA; Tyurin VA; Kagan VE
Mol Nutr Food Res 2013 Aug; 57(8):1410-1422
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. CONCLUSION: 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.
Toxins; Diseases; Exposure-levels; Risk-factors; Neurotoxic-effects; Neurotoxicity; Neurotoxins; Epidemiology; Toxicology; Lymphocytes; Laboratory-animals; Animals; Biomarkers;
Author Keywords: Apoptosis; Cardiolipin peroxidation; Lymphocytes; Mitochondrial dysfunction; Parkinsons disease biomarkers
Dr. Valerian E. Kagan, Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Bridgeside Point, 100 Technology Drive, Suite 350, Pittsburgh, PA 15219
Molecular Nutrition & Food Research
University of Pittsburgh at Pittsburgh