Possible role of enhanced microtubule phosphorylation in dichlorvos induced delayed neurotoxicity in rat

The effect of a single subcutaneous dose of 200 mg/kg body weight dichlorvo s on neuronal microtubule phosphorylation has been studied in rat following the development of organophosphate induced delayed neurotoxicity (OPIDN). Microtubule associated Ca2+/ calmodulin dependent as well as cAMP dependent protein kinases were assayed. Dichlorvos administration led to a consisten t increase in the activity of both the kinases at an post exposure interval s (7th, 15th and 21st day) as compared to that of controls. After in vitro phosphorylation using [gamma-P-32]ATP, various proteins were resolved on on e-dimensional 8% SDS-PAGE, stained with Coomassie Blue and autoradiographed . The amount of P-32 incorporated was quantified by microdensitometry. Dich lorvos enhanced the phosphorylation of 55- and 280-kDa proteins. These two proteins were identified as tubulin and microtubule associated protein-2 (M AP-2) by immunoblotting. This study showed that dichlorvos induced hyperpho sphorylation of tubulin and MAP-2 which in turn destabilizes microtubule as sembly, and may ultimately result in axonal degeneration leading to dichlor vos induced delayed neurotoxicity. (C) 2001 Elsevier Science B.V. All right s reserved.