LC/MS analysis of cardiolipins in substantia nigra and plasma of rotenone-treated rats: implication for mitochondrial dysfunction in Parkinson's disease

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• Personal Author:
  Bayir H ; Domingues MRM ; Greenamyre JT ; Kagan VE ; Kapralova VI ; Maciel E ; McCoy J ; Polimova AM ; Sanders LH ; Tyurin VA ; Tyurina YY ; Vikulina AS ; Winnica DE
• Description:
  Exposure to rotenone in vivo results in selective degeneration of dopaminergic neurons and development of neuropathologic features of Parkinson's disease (PD). As rotenone acts as an inhibitor of mitochondrial respiratory complex I, we employed oxidative lipidomics to assess oxidative metabolism of a mitochondria-specific phospholipid, cardiolipin (CL), in substantia nigra (SN) of exposed animals. We found a significant reduction in oxidizable polyunsaturated fatty acid (PUFA)-containing CL molecular species. We further revealed increased contents of mono-oxygenated CL species at late stages of the exposure. Notably, linoleic acid in sn-1 position was the major oxidation substrate yielding its mono-hydroxy- and epoxy-derivatives whereas more readily "oxidizable" fatty acid residues (arachidonic and docosahexaenoic acids) remained non-oxidized. Elevated levels of PUFA CLs were detected in plasma of rats exposed to rotenone. Characterization of oxidatively modified CL molecular species in SN and detection of PUFA-containing CL species in plasma may contribute to better understanding of the PD pathogenesis and lead to the development of new biomarkers of mitochondrial dysfunction associated with this disease. [Description provided by NIOSH]
• Subjects:
  Acids Biomarkers Energy Metabolism Environmental Monitoring Enzymes Laboratories Lipids Mass Spectrometry Nervous System Nervous System Diseases Nervous System Disorders Occupational Health Oxidants Safety

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• Keywords:
  Author Keywords: Parkinson's Disease Brain-function Brain-matter Cardiolipin Cell-metabolism Cellular-function Cellular-respiration Cellular-structures Central-nervous-system-disorders Energy-metabolism Enzymatic-effects Enzyme-inhibitors Exposure-assessment Fatty-acids In-vivo-study Laboratory-animals Laboratory-techniques Laboratory-testing Liquid-chromatography Mass-spectrometry Molecular-structure Nervous-system-disorders Neurological-diseases Neuromotor-system-disorders Neuropathology Oxidation-reduction-reactions Oxidative-enzymes Oxidative-metabolism Oxidative-processes Oxygenated Cardiolipin Species Oxygenated Linoleic Acid Phospholipids

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• ISSN:
  1071-5762
• 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:
  49
• Issue:
  5
• NIOSHTIC Number:
  nn:20047495
• Citation:
  Free Radic Res 2015 May; 49(5):681-691
• Contact Point Address:
  Yulia Y. Tyurina, PhD, 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. USA
• Email:
  yyt1@pitt.edu
• CAS Registry Number:
  Arachidonic acid (CAS RN 506-32-1) ; Linoleic acid (CAS RN 60-33-3) ; Rotenone (CAS RN 83-79-4)
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Free Radical Research
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c8c3a0eb7839cdbc1f162427cd7340288842b4ae4ed396ae753bea3fe51afeb4ad4c869d43379aa56a4a07d84a166c201b733b7efbadda8453fd3ce1d6cd7efa
• Download URL:
  https://stacks.cdc.gov/view/cdc/202548/cdc_202548_DS1.pdf
• File Type:
  [PDF - 2.34 MB ]