INIBIOLP   05426
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE LA PLATA "PROF. DR. RODOLFO R. BRENNER"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
LOW DOSES OF DIMETHOATE ALTERS CARDIOLIPIN METABOLISM AND INDUCED APOPTOSIS IN RAT BRAIN
Autor/es:
ASTIZ, MARIANA; ALANIZ, MARÍA J.T. DE; MARRA CARLOS ALBERTO
Lugar:
Sevilla
Reunión:
Congreso; 22nd IUBMB (International Union of Biochemistry and Molecular Biology) & 37th FEBS (Federation of European Biochemical Societies) Congress; 2012
Institución organizadora:
FEBS
Resumen:
LOW DOSES OF DIMETHOATE ALTERS CARDIOLIPIN METABOLISM AND INDUCED APOPTOSIS IN RAT BRAIN Astiz, Mariana, Alaniz, M.J.Tacconi de, Marra, Carlos Alberto INIBIOLP, CCT-CONICET, Fac. Ciencias Médicas-UNLP. 60 y 120, 1900, La Plata, Argentina. e-mail: marianaastiz@gmail.com 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. D also affect the inner mitochondrial membrane integrity reducing the electrochemical potential between 30 to 60% compared to controls; this effect correlates with a decrease of mitochondial 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), the 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.  Both effects were observed mainly in SN. Since the close relationship between, the decrease of CL and the induction of apoptosis, 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.