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

Authors
Tyurina-YY; Winnica-DE; Kapralova-VI; Kapralov-AA; Tyurin-VA; Kagan-VE
Source
Mol Nutr Food Res 2013 Aug; 57(8):1410-1422
NIOSHTIC No.
20044123
Abstract
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.
Keywords
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
Contact
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
CODEN
MNFRCV
CAS No.
83-79-4
Publication Date
20130801
Document Type
Journal Article
Email Address
kagan@pitt.edu
Funding Type
Grant
Fiscal Year
2013
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008282
Issue of Publication
8
ISSN
1613-4125
Source Name
Molecular Nutrition & Food Research
State
PA
Performing Organization
University of Pittsburgh at Pittsburgh
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