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Rotenone-induced oxidized molecular species of cardiolipin in human lymphocytes: can they be used as biomarkers of mitochondrial dysfunction associated with Parkinson's disease?
Amoscato-A; Feng-W; Kagan-VE; Tyurina-Y
Toxicologist 2012 Mar; 126(Suppl 1):529
During the last three decades, epidemiological and toxicological studies have provided data that pesticides, including rotenone, contribute to the development of Parkinson's disease (PD). Circulating lymphocytes are often used to study the pathogenic mechanisms in PD. We reasoned that oxidized molecular species of cardiolipin (CL) in human lymphocytes will progressively accumulate in the course of exposure to rotenone. We isolated lymphocytes from human blood obtained from the Central Blood Bank. Using an oxidative lipidomics approach based on 2D-LC/ESI-MS, we found that CL in human lymphocytes was represented mainly by readily oxidizable species containing polyunsaturated fatty acid residues. The contents of CL molecular species with polyunsaturated fatty acid residues - C18:2, C20:4 and C22:6 - were as high as 67.7%, 24.7% and 5.4%, respectively. Only a small amount (2.2% of total CL) of non-oxidizable CL molecular species containing C18:1 was found in human lymphocytes. Detailed structural characterization of oxygenated CL molecular species in lymphocytes treated with rotenone (250 microM, for 18h) revealed the presence of oxidized CL molecular species. Their characterization demonstrated that oxidized CL was represented by a profile containing 13 different hydroxy- and hydroperoxy-molecular species. Further studies of specificity of rotenone induced CL oxidation in rat midbrain and correlations with the unique stereo-specific molecular species of CL formed in mitochondria of human and rat lymphocytes in response to rotenone exposure will determine the extent to which these profiles of lymphocyte CL oxidation may lead to reliable biomarkers of mitochondrial dysfunction associated with neurodegenerative disorders.
Pesticides; Lymphatic-system; Lymphocytes; Humans; Blood-samples; Pathology; Oxidative-processes; Lipids; Fatty-acids; Molecular-biology; Hydroxy-compounds; Oxidation; Exposure-assessment; Laboratory-testing; Biomarkers; Blood-analysis; Blood-tests; Cell-alteration; Cell-damage; Neurological-diseases
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
University of Pittsburgh at Pittsburgh