Low-dose radiation exposure induces a HIF-1-mediated adaptive and protective metabolic response
Low-dose radiation exposure induces a HIF-1-mediated adaptive and protective metabolic response
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DOI：
10.1038/cdd.2014.24
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发表时间：
2014-05-01
影响因子：
12.4
通讯作者：
Yuan, Z-M
中科院分区：
文献类型：
--
作者：
Lall, R.;Ganapathy, S.;Yuan, Z-M
由于对低水平辐射暴露的分子效应了解不够，其健康风险存在很大的不确定性。我们在此报告，用低剂量辐射处理正常人体细胞会诱导代谢从氧化磷酸化转变为有氧糖酵解，从而导致辐射抵抗力增强。这种代谢变化通过编码葡萄糖转运蛋白和糖酵解酶以及氧化戊糖磷酸途径的基因的上调而突出，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，代谢重编程依赖于 HIF1 α，它是由低剂量辐射特异性诱导的，将代谢途径与细胞辐射剂量反应联系起来。在小鼠中也观察到低剂量照射导致的葡萄糖通量增加和辐射抗性增加。这种对低剂量辐射的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。
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.