Hypoxic stress is linked to various cardiovascular disorders (e.g., stroke, myocardial infarction), mediated, at least in part, by a reduction in ATP synthesis. Fructose‐driven glycolysis is proposed as an alternative pathway capable of sustaining ATP production even under anoxic conditions. Here, we tested the hypothesis that facilitating fructose‐driven metabolism exerts a protective effect against anoxic stress in Drosophila. Genetically modified flies with the human fructose transporter (GluT5) and ketohexokinase (KHK) genes downstream of upstream activating sequence (UAS) were constructed. The GAL4‐UAS system was confirmed to: (i) increase the expression of GluT5 and KHK in a tissue‐specific and a time‐dependent manner (i.e., whole flies [with Act5c‐gene switch GAL4 driver], neurons [with elav‐gene switch GAL4 driver]) and (ii) reduce mortality of flies when placed under anoxic stress. Taken together, these data suggest that increasing fructose metabolism may be a clinically relevant approach to minimize hypoxia‐induced cellular damage.

中文翻译：

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促进果糖驱动的代谢对果蝇的缺氧应激产生保护作用。

缺氧应激与各种心血管疾病（例如中风、心肌梗塞）有关，至少部分是由 ATP 合成减少介导的。果糖驱动的糖酵解被提议作为一种替代途径，即使在缺氧条件下也能维持 ATP 的产生。在这里，我们测试了促进果糖驱动的代谢对果蝇缺氧应激产生保护作用的假设. 构建了在上游激活序列 (UAS) 下游具有人类果糖转运蛋白 (GluT5) 和酮己糖激酶 (KHK) 基因的转基因果蝇。GAL4-UAS 系统被证实：(i) 以组织特异性和时间依赖性方式增加 GluT5 和 KHK 的表达（即，整只果蝇[带有 Act5c 基因开关 GAL4 驱动程序]，神经元 [带有 elav-基因开关 GAL4 驱动程序]) 和 (ii) 在缺氧压力下降低果蝇的死亡率。总之，这些数据表明增加果糖代谢可能是一种临床相关的方法，可以最大限度地减少缺氧引起的细胞损伤。