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 MARIA J. TACCONI DE; MARRA CARLOS ALBERTO
Lugar:
Sevilla
Reunión:
Congreso; IUBMB (International Union of Biochemistry and Molecular Biology) & 37th FEBS (Federation of European Biochemical Societies); 2013
Institución organizadora:
IUBMB (International Union of Biochemistry and Molecular Biology
Resumen:
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% and 60% compared to controls; this effect correlates with a decrease of mitochondia l
cardiolipin (CL) from 30% to 50% and with an increase of mono-lyso CL (MLCL) between 25% and 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 Dinduced 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