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

Details

• Personal Author:
  Kagan VE ; Kapralov AA ; Kapralova VI ; Tyurin VA ; Tyurina YY ; Winnica DE
• 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. 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. [Description provided by NIOSH]
• Subjects:
  Animals Biomarkers Blood Epidemiology Hazardous Substances Laboratories Nervous System Occupational Health Risk Assessment Risk Factors Safety Toxicology

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• Keywords:
  Author Keywords: Apoptosis Cardiolipin Peroxidation Diseases Exposure-levels Laboratory-animals Lymphocytes Mitochondrial Dysfunction Neurotoxic-effects Neurotoxicity Neurotoxins Parkinsons Disease Biomarkers Risk-factors Toxins

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• ISSN:
  1613-4125
• 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
• Volume:
  57
• Issue:
  8
• NIOSHTIC Number:
  nn:20044123
• Citation:
  Mol Nutr Food Res 2013 Aug; 57(8):1410-1422
• Contact Point Address:
  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
• Email:
  kagan@pitt.edu
• CAS Registry Number:
  Rotenone (CAS RN 83-79-4)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Molecular Nutrition & Food Research
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:22c34bf4465ae020b09116b235202e012f0b1540674ecf1280713f1b287f59f35b74b08f49927e608ccabe8fa9fade98d0023d4fcf41306b0db4d3c184858a71
• Download URL:
  https://stacks.cdc.gov/view/cdc/199946/cdc_199946_DS1.pdf
• File Type:
  [PDF - 885.38 KB ]