The organophosphorus insecticide dimethoate alters mitochondrial lipid metabolism in rat brain

ASTIZ, MARIANA; ALANIZ, MARIA J.T. DE; MARRA, CARLOS A.

Miami, FL

Congreso; 2013 Miami Winter Symposium (The Molecular Basis of metabolism and Nutrition); 2013

Organizado por University of Miami, IUBMB

The widely used insecticide, dimethoate (D), was administered for 5 weeks (subchronic) at low dose (15 mg/Kg) to male Wistar rats with the aim to simulate the exposure to pesticide residues in food. In brain, D administration provoked oxidative stress, increased the expression of caspase-3 in substantia nigra (SN) and the expression and activity of mili- and micro- calpains in cerebral cortex (CC) and SN, we also found a higher ratio Bax/Bcl-2 and a significant release of cytochrome C (CytC) from mitochondria (M) in both brain regions compared to controls (Astiz et al., Ecotoxicol. Environ. Saf. 2009,72:2025-32). D also affect mitochondrial morphology (modifying the expression of fusion/fission proteins such as Mfn2 and Drp1) and mitochondrial inner membrane integrity reducing the electrochemical potential between 30 to 60% compared to controls; the latter effect correlates with a decrease of mitochondrial cardiolipin (CL) from 30 to 50% and with an increase of mono-lyso CL (MLCL) between 25 to 40%. CL is rich in polyunsaturated fatty acids (PUFAs) and it composition varies greatly within brain regions. The decrease could be associated to the oxidative damage of their fatty acyl chains, D-treatment caused an increase of 18:0 and a decrease of PUFAs (18:2, 20:4, 22:5, 22:6) in CL and MLCL (except the ratio 18:0/18:1 which is higher in MLCL). These changes could be due to the remodeling action of PLA2/AcilCoA-Acetilase on the peroxidated CL pool and could explain the D-dependent decrease in CL content and also the release of CytC from M (Claypool and Koehler, Trends Biochem. Sci. 2011, 37:32-41). Both effects were observed mainly in SN. Since the close relationship between the mitochondrial morphology and CL decrease, with the induction of apoptosis (Pope et al., Biochim. Biophys. Acta 2008, 1777:794-9), we proposed that D-induced oxidation of CL fatty acids could be at least one of the toxic mechanisms of D as an environmental pollutant. The results could contribute to understand the etiological role that pesticide residues in food could play in neurodegenerative diseases.