Hypoxia and nitric oxide treatment confer tolerance to glucose starvation in a 5′-AMP-activated protein kinase-dependent manner
Hypoxia and nitric oxide treatment confer tolerance to glucose starvation in a 5′-AMP-activated protein kinase-dependent manner
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DOI：
10.1074/jbc.m112270200
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发表时间：
2002-09-06
影响因子：
4.8
通讯作者：
Ozawa, T
中科院分区：
文献类型：
--
作者：
Esumi, H;Izuishi, K;Ozawa, T
缺氧是高等生物的关键事件，细胞和组织通过血管舒张、血管生成和红细胞生成增加氧供应，并通过增加糖酵解和抑制合成代谢途径维持细胞能量来反应。糖酵解的刺激被认为是在缺氧期间增加能量产生的主要反应;然而，在缺血期间存在明显的冲突，因为氧气和葡萄糖供应都不足。在这项研究中，我们发现暴露于缺氧的HepG 2细胞和正常的成纤维细胞诱导细胞耐受葡萄糖饥饿。缺氧诱导的耐受依赖于几种氨基酸，表明从葡萄糖到氨基酸作为能量来源的转换。将5 '-AMP激活的蛋白激酶或蛋白激酶B/Akt的反义RNA转染HepG 2细胞后，可明显抑制HepG 2细胞对葡萄糖耐受的诱导作用，表明葡萄糖耐受依赖于5'-AMP激活的蛋白激酶和蛋白激酶B/Akt。类似的耐受性诱导一氧化氮暴露。在各种细胞中观察到诱导的耐受性，并且可能代表与缺氧预处理和肿瘤进展相关的先前未知的生理反应：紧缩。
Hypoxia is a critical event for higher organisms, and cells and tissues react by increasing the oxygen supply by vasodilatation, angiogenesis, and erythropoiesis and maintaining cellular energy by increasing glycolysis and inhibiting anabolic pathways. Stimulation of glycolysis has been regarded as the main response that increases energy production during hypoxia; however, there is an obvious conflict during ischemia, because both the oxygen and glucose supply are insufficient. In this study, we found that exposure of HepG2 cells and normal fibroblasts to hypoxia induces cellular tolerance to glucose starvation. The tolerance induced by hypoxia is dependent on several amino acids, indicating a switch from glucose to amino acids as the energy source. When antisense RNA expression vector for 5'-AMP-activated protein kinase or protein kinase B/Akt was transfected into HepG2 cells, the induction of tolerance to glucose was greatly inhibited, indicating that the tolerance was dependent on 5'-AMP-activated protein kinase and protein kinase B/Akt. Similar tolerance was induced by nitric oxide exposure. The tolerance induced was observed in various cells and may represent a previously unknown physiological response related to hypoxia-preconditioning and tumor progression:austerity.