Adenosine (Ado) is an important signaling molecule involved in stress responses. Studies in mammalian models have shown that Ado regulates signaling mechanisms involved in 'danger-sensing' and tissue-protection. Yet, little is known about the role of Ado signaling in Drosophila. In the present study, we observed lower extracellular Ado concentration and suppressed expression of Ado transporters in flies expressing mutant huntingtin protein (mHTT). We altered Ado signaling using genetic tools and found that the overexpression of Ado metabolic enzymes, as well as the suppression of Ado receptor (AdoR) and transporters (ENTs), were able to minimize mHTT-induced mortality. We also identified the downstream targets of the AdoR pathway, the modifier of mdg4 (Mod(mdg4)) and heat-shock protein 70 (Hsp70), which carry out its function. Finally, we showed that a decrease in Ado signaling affect other Drosophila stress reactions, including paraquat and heat-shock treatments. Our study provides important insights into how Ado regulates stress responses in Drosophila.

中文翻译：

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腺苷受体及其下游靶标mod（mdg4）和Hsp70，是调节果蝇细胞毒性损伤的信号传导途径

腺苷（Ado）是参与应激反应的重要信号分子。哺乳动物模型的研究表明，Ado调节涉及“危险感知”和组织保护的信号传导机制。然而，人们对Ado信号在果蝇中的作用知之甚少。在本研究中，我们观察到较低的细胞外Ado浓度并抑制了表达突变亨廷顿蛋白（mHTT）的果蝇中Ado转运蛋白的表达。我们使用遗传工具改变了Ado信号传导，发现Ado代谢酶的过表达以及Ado受体（AdoR）和转运蛋白（ENTs）的抑制能够最大程度地降低mHTT诱导的死亡率。我们还确定了AdoR途径的下游目标，mdg4的修饰子（Mod（mdg4））和热休克蛋白70（Hsp70），它们可以发挥其功能。最后，我们发现，Ado信号的降低会影响其他果蝇应激反应，包括百草枯和热休克疗法。我们的研究为Ado如何调节果蝇的应激反应提供了重要的见识。