Glutathione transferase modulates acute ethanol‐induced sedation in Drosophila neurones

• Published in: Insect molecular biology Vol. 28; no. 2; pp. 246 - 252
• Main Authors: Choi, H.‐J., Cha, S. J., Kim, K.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-04-2019
• Subjects: alcohol; Alcohols; Animals; Central Nervous System Depressants - toxicity; Dopamine receptors; Drosophila; Drosophila - drug effects; Drosophila - enzymology; Drosophila - genetics; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Ethanol; Ethanol - toxicity; ethanol sedation; Gene expression; Glutathione; Glutathione transferase; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; glutathione transferase omega; Insects; Male; neurone; Neurons - drug effects; Ribonucleic acid; RNA; RNA-mediated interference; Sensitivity; Serotonin; Toxicity; alcohol; glutathione transferase omega; Drosophila; ethanol sedation; neurone
• ISSN: 0962-1075; 1365-2583
• DOI: 10.1111/imb.12547

Heavy alcohol consumption leads to neuropathological damage and alcohol use disorder, which affects the health of people and results in a cost burden. However, the genes modulating sensitivity to ethanol remain largely unknown. Here, we identified a novel gene, Drosophila glutathione transferase omega 1 (GstO1), which plays a critical role in regulating sensitivity to ethanol sedation. GstO1 mutant flies showed highly increased ethanol sensitivity. Furthermore, the expression level of GstO1 regulates the behavioural response to ethanol, because decreasing and increasing GstO1 affects sedation sensitivity in a contrasting manner. In addition, the RNA interference‐mediated knockdown of GstO1 expression reveals that GstO1 mediates sensitivity to ethanol sedation in neurones, including dopaminergic and serotonergic neurones. Altogether, our findings provide the first evidence for the involvement of glutathione transferase in the response to alcohol in Drosophila and provide a novel mechanistic insight into the toxicity and sensitivity of ethanol exposure.