title: Overexpression of hsp27 Rescued Neuronal Cell Death and Reduction in Life- and Health-Span in Drosophila melanogaster Against Prolonged Exposure to Dichlorvos.
abstract: Long-term exposure to dichlorvos (O,O-dimethyl-2,2-dichlorovinyl phosphate (DDVP), an organophosphate pesticide) is reported to exert neurotoxicity, i.e., generation of reactive oxygen species (ROS), oxidative damage, and neuronal cell death along with life- and health-span reduction in nontarget organisms including humans. However, studies on genetic modulation towards neuroprotection against prolonged DDVP exposure are elusive. Hsp27 (a small heat shock protein) is involved in various cellular processes and thus has attained emphasis as a therapeutic target. We aimed to examine the protective effect of hsp27 overexpression against prolonged DDVP exposure using an in vivo model Drosophila melanogaster. Flies were exposed to 15.0 ng/ml DDVP for a prolonged period to examine neuronal cell death, locomotor performance, and lifespan. After prolonged exposure, cell death, ROS level, glutathione depletion, nicotinamide adenine dinucleotide phosphate level (NADPH), glucose-6-phosphate dehydrogenase (G6PD), and thioredoxin reductase (TrxR) activities were examined in fly brain tissues at different days of age (days 10, 20, and 30). Flies with ubiquitous overexpression of hsp27 showed better resistance (improved lifespan and locomotor performance) in comparison to that targeted to motor neurons and nervous system. These flies also exhibited lesser intracellular ROS level and glutathione depletion by restoring G6PD activity, NADPH level, and TrxR activity in their brains thereby resisted neuronal cell death. Conversely, hsp27 knockdown flies exhibited reversal of the above endpoints. The study evidenced the neuroprotective efficacy of hsp27 overexpression against prolonged DDVP exposure and favored Hsp27 as a therapeutic target towards achieving better organismal (including human) health against long-term chemical exposure.
authors.affiliation: Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India.|Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Pandey
authors.affiliation: Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Saini
authors.affiliation: Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India.
authors.forename: Rehana
authors.initials: R
authors.lastname: Khatoon
authors.affiliation: Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India.|Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Sharma
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
authors.forename: Gopeshwar
authors.initials: G
authors.lastname: Narayan
authors.affiliation: Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India. dkchowdhuri@iitr.res.in.|Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, India. dkchowdhuri@iitr.res.in.
authors.forename: Debapratim
authors.initials: D
authors.lastname: Kar Chowdhuri
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004006:Dichlorvos / Q000633:toxicity*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007305:Insecticide Resistance / Q000187:drug effects; D008136:Longevity / Q000187:drug effects*; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects; D009249:NADP / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002800:Cholinesterase Inhibitors; D029721:Drosophila Proteins; D006360:Heat-Shock Proteins; C087442:Hsp26 protein, Drosophila; D017382:Reactive Oxygen Species; D009249:NADP; D004006:Dichlorvos; D005978:Glutathione
keywords: Dichlorvos; Drosophila; Health-span; Lifespan; Neuronal cell death; Prolonged exposure; hsp27