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Low-dose radiation exposure induces a HIF-1-mediated adaptive and protective metabolic response

机译:低剂量辐射诱导HIF-1介导的适应性和保护性代谢反应

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摘要

Because of insufficient understanding of the molecular effects of low levels of radiation exposure, there is a great uncertainty regarding its health risks. We report here that treatment of normal human cells with low-dose radiation induces a metabolic shift from oxidative phosphorylation to aerobic glycolysis resulting in increased radiation resistance. This metabolic change is highlighted by upregulation of genes encoding glucose transporters and enzymes of glycolysis and the oxidative pentose phosphate pathway, concomitant with downregulation of mitochondrial genes, with corresponding changes in metabolic flux through these pathways. Mechanistically, the metabolic reprogramming depends on HIF1 alpha, which is induced specifically by low-dose irradiation linking the metabolic pathway with cellular radiation dose response. Increased glucose flux and radiation resistance from low-dose irradiation are also observed systemically in mice. This highly sensitive metabolic response to low-dose radiation has important implications in understanding and assessing the health risks of radiation exposure.
机译:由于对低水平辐射暴露的分子效应了解不足,因此对其健康风险存在很大的不确定性。我们在这里报告,低剂量辐射对正常人细胞的治疗诱导了从氧化磷酸化到有氧糖酵解的代谢转变,从而导致辐射抗性增加。这种代谢变化通过编码葡萄糖转运蛋白和糖酵解酶的基因的上调以及氧化性戊糖磷酸途径而突出,同时伴随着线粒体基因的下调,以及通过这些途径的代谢通量的相应变化。从机制上讲,代谢重编程取决于HIF1α,它是由低剂量辐射(将代谢途径与细胞辐射剂量反应相关联)特异性诱导的。还可以在小鼠中全身观察到低剂量辐照增加的葡萄糖通量和抗辐射性。对低剂量辐射的这种高度敏感的代谢反应对于理解和评估辐射暴露的健康风险具有重要意义。

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