Oxidized cardiolipins as a biomarker of mitochondrial dysfunction triggered by pesticide, rotenone.
Tyurina Y; Vikulina A; Kapralova V; Winnica D; Sanders L; Greenamyre T; Tyurin VA; Kagan VE
Toxicologist 2014 Mar; 138(1):398
Exposure to a commonly used pesticide, rotenone, has been associated with the development of Parkinson's disease. We demonstrated that treatment of human blood lymphocytes with rotenone resulted in decreased mitochondrial membrane potential, inhibition of mitochondrial respiratory complex I, induction of apoptosis and selective oxidation of mitochondrial phospholipid, cardiolipin (CL). Here, we used rat rotenone-infusion Parkinson disease model to assess possible accumulation of peroxidized phospholipids. Adult male Lewis rats (6 months old) were exposed to rotenone daily (3 mg/kg, I.P.) and sacrificed 1, 5 and 10-14 days thereafter. Substantia nigra was isolated and lipids were extracted. To enhance the sensitivity of LC-MS protocols for the detection of oxidation products, phospholipids were treated either with phospholipase A1 from Thermomyces lanuginosus (10 ml/mmol phospholipids) or phospholipase A2 form porcine pancreas (10U/ mmol of phospholipids) to release fatty acids residues from sn-1 and sn-2 position, respectively. Using the combination of lipidomics and oxidative epitope-targeted enzymatic digestion of total phospholipids we found a decrease of polyunsaturated fatty acids (PUFA) esterified into phospholipids on day 1 and 5 after expose. In addition we were able to detect oxygenated species of PUFA that were represented by their hydroxy-derivatives. Moreover, a decrease of CL species containing PUFA and accumulation of its oxygenated molecular species was oserved. We conclude that CL oxygenation products may represent a new biomarker of rotenone-induced mitochondrial dysfunction associated with Parkinson disease.
Toxicology; Exposure-levels; Environmental-exposure; Pathology; Animals; Laboratory-animals; Pesticides; Blood-cells; Neurological-diseases; Neurological-reactions; Nervous-system-disorders
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona
University of Pittsburgh at Pittsburgh