title: Induction of hsp70, alterations in oxidative stress markers and apoptosis against dichlorvos exposure in transgenic Drosophila melanogaster: modulation by reactive oxygen species.
abstract: We examined a hypothesis that reactive oxygen species (ROS) generated by organophosphate compound dichlorvos modulates Hsp70 expression and anti-oxidant defense enzymes and acts as a signaling molecule for apoptosis in the exposed organism. Dichlorvos (0.015-15.0 ppb) without or with inhibitors of Hsp70, superoxide dismutase (SOD) and catalase (CAT) were fed to the third instar larvae of Drosophila melanogaster transgenic for hsp70 (hsp70-lacZ) Bg(9) to examine Hsp70 expression, oxidative stress and apoptotic markers. A concentration- and time-dependent significant increase in ROS generation accompanied by a significant upregulation of Hsp70 preceded changes in antioxidant defense enzyme activities and contents of glutathione, malondialdehyde and protein carbonyl in the treated organisms. An inhibitory effect on SOD and CAT activities significantly upregulated ROS generation and Hsp70 expression in the exposed organism while inhibition of Hsp70 significantly affected oxidative stress markers induced by the test chemical. A comparison made among ROS generation, Hsp70 expression and apoptotic markers showed that ROS generation is positively correlated with Hsp70 expression and apoptotic cell death end points indicating involvement of ROS in the overall adversity caused by the test chemical to the organism. The study suggests that (a) Hsp70 and anti-oxidant enzymes work together for cellular defense against xenobiotic hazard in D. melanogaster and (b) free radicals may modulate Hsp70 expression and apoptosis in the exposed organism.
authors.affiliation: Embryotoxicology Section, Industrial Toxicology Research Centre, P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow-226 001, Uttar Pradesh, India.
authors.forename: Subash Chandra
authors.initials: SC
authors.lastname: Gupta
authors.forename: Hifzur Rahman
authors.initials: HR
authors.lastname: Siddique
authors.forename: Neeraj
authors.initials: N
authors.lastname: Mathur
authors.forename: Achchhe Lal
authors.initials: AL
authors.lastname: Vishwakarma
authors.forename: Ranjit Kishore
authors.initials: RK
authors.lastname: Mishra
authors.forename: Daya Krishna
authors.initials: DK
authors.lastname: Saxena
authors.forename: Debapratim Kar
authors.initials: DK
authors.lastname: Chowdhuri
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004006:Dichlorvos / Q000494:pharmacology*; D004331:Drosophila melanogaster; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D007814:Larva / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008315:Malondialdehyde; D004006:Dichlorvos; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D053148:Caspase 3; D053453:Caspase 9; D005978:Glutathione