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

24 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Dichlorvos
Microtubules
Phosphorylation
Microtubule-Associated Proteins
Tubulin
Proteins
Organophosphates
Calmodulin
Cyclic AMP-Dependent Protein Kinases
Immunoblotting
Polyacrylamide Gel Electrophoresis
Phosphotransferases
Adenosine Triphosphate
Body Weight

Keywords

  • Delayed neurotoxicity
  • Dichlorvos
  • Microtubule
  • Phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Possible role of enhanced microtubule phosphorylation in dichlorvos induced delayed neurotoxicity in rat. / Choudhary, Sanjeev; Joshi, Kusum; Gill, Kiran Dip.

In: Brain Research, Vol. 897, No. 1-2, 06.04.2001, p. 60-70.

Research output: Contribution to journalArticle

Choudhary, Sanjeev ; Joshi, Kusum ; Gill, Kiran Dip. / Possible role of enhanced microtubule phosphorylation in dichlorvos induced delayed neurotoxicity in rat. In: Brain Research. 2001 ; Vol. 897, No. 1-2. pp. 60-70.
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