生命的低氧适应——2019年度诺贝尔生理学或医学奖成果解析

Hypoxia adaption in life——An analysis of Nobel Prize in Physiology or Medicine in 2019

氧的利用和调节是高等生命赖以生存的基本条件,威廉·凯林、彼得·拉特克利夫和格雷格·塞门扎3位科学家因发现细胞感知和适应氧气供应的相关机制而获得了2019年度诺贝尔生理学或医学奖。他们发现低氧诱导因子1(hypoxia-inducible factors 1,HIF-1)广泛存在于急、慢性缺氧细胞中,是细胞适应低氧的重要转录因子。HIF-1水平受氧气含量的调节。高氧条件下,HIF-1被修饰进而降解;低氧条件下,HIF-1不被降解,并通过转录调节引起促红细胞生成素等低氧相关基因的表达。本文通过介绍HIF-1的发现和基本分子机制,探讨其在临床中的应用价值。

Using and adjusting the oxygen is the basic condition for higher organisms.Three British and American scientists,William G.Kaelin Jr,Sir Peter J.Ratcliffe and Gregg L.Semenza,won the Nobel Prize in physiology or medicine in 2019 for discovering the mechanisms by which cells sense and adapt to the oxygen.They have found that the hypoxia inducible factor 1(HIF-1),an important transcription factor,is widely distributed in chronic hypoxic cells and promotes cells to adapt to the hypoxia.The HIF-1 level is regulated by the oxygen content.Under the high oxygen condition,the HIF-1 is degraded after its modification.Conversely,under the low oxygen condition,the HIF-1 is not degraded and promotes the expression of the hypoxia related genes such as the erythropoietin through the transcriptional regulation.This paper reviews the discovery and the basic molecular mechanism of the HIF-1,as well as its clinical application values.