title: LC/MS characterization of rotenone induced cardiolipin oxidation in human lymphocytes: implications for mitochondrial dysfunction associated with Parkinson's disease.
abstract: METHODS
  Rotenone is a toxicant believed to contribute to the development of Parkinson's disease.
  
  
  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.
authors: Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15219, USA. yyt1@pitt.edu
authors: Yulia Y
authors: YY
authors: Tyurina
authors: Daniel E
authors: DE
authors: Winnica
authors: Valentina I
authors: VI
authors: Kapralova
authors: Alexandr A
authors: AA
authors: Kapralov
authors: Vladimir A
authors: VA
authors: Tyurin
authors: Valerian E
authors: VE
authors: Kagan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002308:Cardiolipins / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism; D013058:Mass Spectrometry; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity*
chemical_list: D002308:Cardiolipins; D008246:Lysophospholipids; D017382:Reactive Oxygen Species; C067188:monolysocardiolipin; C523441:tetralinoleoylcardiolipin; D012402:Rotenone; D010544:Peroxidases
keywords: Apoptosis; Cardiolipin peroxidation; Lymphocytes; Mitochondrial dysfunction; Parkinson's disease biomarkers
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