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

Sanjeev Choudhary, Kusum Joshi, Kiran Dip Gill

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

The effect of a single subcutaneous dose of 200 mg/kg body weight dichlorvos 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 consistent increase in the activity of both the kinases at all post exposure intervals (7th, 15th and 21st day) as compared to that of controls. After in vitro phosphorylation using [γ-32P]ATP, various proteins were resolved on one-dimensional 8% SDS-PAGE, stained with Coomassie Blue and autoradiographed. The amount of 32P incorporated was quantified by microdensitometry. Dichlorvos enhanced the phosphorylation of 55- and 280-kDa proteins. These two proteins were identified as tubulin and microtubule associated protein-2 (MAP-2) by immunoblotting. This study showed that dichlorvos induced hyperphosphorylation of tubulin and MAP-2 which in turn destabilizes microtubule assembly, and may ultimately result in axonal degeneration leading to dichlorvos induced delayed neurotoxicity.

Original languageEnglish (US)
Pages (from-to)60-70
Number of pages11
JournalBrain Research
Volume897
Issue number1-2
DOIs
StatePublished - Apr 6 2001

Keywords

  • Delayed neurotoxicity
  • Dichlorvos
  • Microtubule
  • Phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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