Efficacy of methuselah gene mutation toward tolerance of dichlorvos exposure in Drosophila melanogaster.
Adverse reports on the exposure of organisms to dichlorvos (DDVP; an organophosphate insecticide) necessitate studies of organismal resistance/tolerance by way of pharmacological or genetic means. In the context of genetic modulation, a mutation in methuselah (mth; encodes a class II G-protein-coupled receptor (GPCR)) is reported to extend (~35%) the life span of Drosophila melanogaster and enhance their resistance to oxidative stress induced by paraquat exposure (short term, high level). A lack of studies on organismal tolerance of DDVP by genetic modulation prompted us to examine the protective efficacy of mth mutation in exposed Drosophila. Flies were exposed to 1.5 and 15.0 ng/ml DDVP for 12-48 h to examine oxidative stress endpoints and chemical resistance. After prolonged exposure of flies to DDVP, antioxidant enzyme activities, oxidative stress, glutathione content, and locomotor performance were assayed at various days (0, 10, 20, 30, 40, 50) of age. Flies with the mth mutation (mth(1)) showed improved chemical resistance and rescued redox impairment after acute DDVP exposure. Exposed mth(1) flies exhibited improved life span along with enhanced antioxidant enzyme activities and rescued oxidative perturbations and locomotor insufficiency up to middle age (~20 days) over similarly exposed w(1118) flies. However, at late (≥30 days) age, these benefits were undermined. Further, similarly exposed mth-knockdown flies showed effects similar to those observed in mth(1) flies. This study provides evidence of tolerance in organisms carrying a mth mutation against prolonged DDVP exposure and further warrants examination of similar class II GPCR signaling facets toward better organismal health.
Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow 226001, Uttar Pradesh, India; Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India.
Ashutosh
A
Pandey
Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow 226001, Uttar Pradesh, India.
Rehana
R
Khatoon
Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow 226001, Uttar Pradesh, India.
Sanjay
S
Saini
Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, India.
Divya
D
Vimal
Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, India; Analytical Chemistry Section, CSIR-Indian Institute of Toxicology Research, Lucknow 226001, Uttar Pradesh, India.
Devendra Kumar
DK
Patel
Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India.
Gopeshwar
G
Narayan
Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, India. Electronic address: dkchowdhuri@iitr.res.in.
Debapratim Kar
DK
Chowdhuri
D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000254:growth & development*; D000871:Anthelmintics / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D004006:Dichlorvos / Q000633:toxicity*; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D004361:Drug Tolerance / Q000235:genetics*; D008136:Longevity / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000871:Anthelmintics; D000975:Antioxidants; D029721:Drosophila Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C115381:mth protein, Drosophila; D004006:Dichlorvos
Dichlorvos; Drosophila; Free radicals; Life span; Long-term exposure; Methuselah; Oxidative stress