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首页> 外文期刊>European Journal of Cell Biology: Journal of Deutsche Gesellschaft fur Elektronenmikroskopie: Journal of Deutsche Gesellschaft fur Zellbiologie >Enhanced sensitivity of protein kinase B/Akt to insulin in hypoxia is independent of HIF1alpha and promotes cell viability
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Enhanced sensitivity of protein kinase B/Akt to insulin in hypoxia is independent of HIF1alpha and promotes cell viability

机译:缺氧时蛋白激酶B / Akt对胰岛素的敏感性增强独立于HIF1alpha并促进细胞活力

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摘要

Maintenance of oxygen homeostasis is a key requirement to ensure normal mammalian cell growth and differentiation. Hypoxia arises when oxygen demand exceeds supply, and is a feature of multiple human diseases including stroke, cancer and renal fibrosis. We have investigated the effect of hypoxia on kidney cells, and observed that insulin-induced cell viability is increased in hypoxia. We have characterized the role of protein kinase B (PKB/Akt) in these cells as a potential mediator of this effect. PKB/Akt activity was increased by low oxygen concentrations in kidney cells, and insulin-stimulated activation of PKB/Akt was stronger, more rapid and more sustained in hypoxia. Reduction of HIF1alpha levels using antimycin-A or siRNA targeting HIF1alpha did not affect PKB/Akt activation in hypoxia. Pharmacologic stabilization of HIF1alpha independent of hypoxia did not increase insulin-stimulated PKB/Akt activation. Although increased insulin-stimulated cell viability was observed in hypoxia, no differences in the degree of insulin-stimulated glucose uptake were observed in L6 muscle cells in hypoxia compared to normoxia. Thus, PKB/Akt may regulate specific cellular responses to growth factors such as insulin under adverse conditions such as hypoxia.
机译:维持氧稳态是确保正常哺乳动物细胞生长和分化的关键要求。当氧气需求超过供应时,就会出现缺氧,这是多种人类疾病的特征,包括中风,癌症和肾纤维化。我们研究了缺氧对肾细胞的影响,并观察到缺氧时胰岛素诱导的细胞活力增加。我们已经表征了蛋白激酶B(PKB / Akt)在这些细胞中作为这种作用的潜在介体的作用。肾细胞中的低氧浓度可增加PKB / Akt的活性,而缺氧时胰岛素刺激的PKB / Akt激活更强,更快且更持久。使用抗霉素A或靶向HIF1alpha的siRNA降低HIF1alpha的水平不会影响缺氧时的PKB / Akt激活。独立于缺氧的HIF1alpha药理稳定不会增加胰岛素刺激的PKB / Akt激活。尽管在缺氧状态下观察到胰岛素刺激的细胞活力增加,但是与低氧相比,在低氧状态下L6肌肉细胞中未观察到胰岛素刺激的葡萄糖摄取程度的差异。因此,在诸如缺氧的不利条件下,PKB / Akt可以调节对生长因子(如胰岛素)的特异性细胞应答。

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