Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan, Korea.
Department of Medical Biotechnology, Soonchunhyang University, Asan, Korea.
Insect Mol Biol. 2019 Apr;28(2):246-252. doi: 10.1111/imb.12547. Epub 2018 Nov 19.
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.
大量饮酒会导致神经病理学损伤和酒精使用障碍，从而影响人们的健康，并造成经济负担。然而，调节对乙醇敏感性的基因在很大程度上仍是未知的。在这里，我们鉴定了一个新的基因，果蝇谷胱甘肽 S-转移酶 ω1（GstO1），它在调节对乙醇镇静的敏感性方面起着关键作用。GstO1 突变体果蝇表现出高度增加的乙醇敏感性。此外，GstO1 的表达水平调节对乙醇的行为反应，因为降低和增加 GstO1 以相反的方式影响镇静敏感性。此外，RNA 干扰介导的 GstO1 表达敲低表明 GstO1 在神经元中介导对乙醇镇静的敏感性，包括多巴胺能和 5-羟色胺能神经元。总之，我们的研究结果首次提供了谷胱甘肽转移酶参与果蝇对酒精反应的证据，并为乙醇暴露的毒性和敏感性提供了新的机制见解。
