S. Choudhary et al., Possible role of enhanced microtubule phosphorylation in dichlorvos induced delayed neurotoxicity in rat, BRAIN RES, 897(1-2), 2001, pp. 60-70
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.