Get access

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

Authors

  • Yulia Y. Tyurina,

    Corresponding author
    • Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
    Search for more papers by this author
  • Daniel E. Winnica,

    1. Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
    Search for more papers by this author
  • Valentina I. Kapralova,

    1. Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
    Search for more papers by this author
  • Alexandr A. Kapralov,

    1. Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
    Search for more papers by this author
  • Vladimir A. Tyurin,

    1. Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
    Search for more papers by this author
  • Valerian E. Kagan

    Corresponding author
    • Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
    Search for more papers by this author

Correspondence: 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, USA

E-mail: kagan@pitt.edu

Fax: +1-412-624-9361

Additional corresponding author: Dr. Yulia Y. Tyurina,

E-mail: yyt1@pitt.edu

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.

Ancillary