缺氧信号转导通路的研究进展

The Progress of Study on Cellular Signal Transduction of the Hypoxia Response

人体组织和细胞在环境氧浓度改变的条件下,通过氧感受器和信号转导通路特异地调节某些基因或蛋白的表达来适应低氧。同时在缺氧情况下,缺氧反应导致多种细胞信号通路的激活参与调节呼吸、代谢、细胞生存等。在哺乳动物体内,HIFs是主要的低氧应激转录因子,其α亚基受到多种因素的影响,如PHDs、FIH1、线粒体、CHIP,本文将在常氧和缺氧状态下,对HIF稳定性调节机制及缺氧所介导相关信号转导通路进行综述。

Cells induce the hypoxia responses to adapt to the environment when organisms are exposed to a low oxygen environment.The hypoxia response leads to the activation of multiple cellular signalling pathways involved in regulation of respiration,metabolism,cell survival and so forth.In mammals,the primary transcriptional response to hypoxic stress is mediated by the HIFs.While canonically regulated by PHDs,the HIFa subunits are intricately responsive to numerous other factors,including FIH1,metabolites,and CHIP.This review describes the regulatory mechanism of HIF stability and activity under normoxia and hypoxic conditions.Furthermore,the role of the HIF-independent pathways during the hypoxia response,which is as important as the HIF pathway,will also be described.