GLTSCR2使细胞对缺氧损伤敏感，而不涉及线粒体凋亡级联反应。
GLTSCR2 sensitizes cells to hypoxic injury without involvement of mitochondrial apoptotic cascades.
作者信息
Yim Ji-Hye, Kim Yong-Jun, Cho Young-Eun, Ko Jeong-Hun, Kim Su-Mi, Kim Jee-Youn, Park Jae-Hoon
机构信息
Department of Pathology and Medical Research Center for Bioreaction to Reactive Oxygen Species, College of Medicine, Kyung Hee University, Seoul, Korea.
出版信息
Pathobiology. 2007;74(5):301-8. doi: 10.1159/000105813.
OBJECTIVE
We attempted to identify novel genes that induce hypoxic cell death to better understand the molecular mechanisms underlying hypoxia-induced cell death. Through this process the GLTSCR2 gene was found. The purpose of this work was to investigate the role of GLTSCR2 in hypoxic cell death pathways.
METHODS
This work focuses on an investigation of roles and mechanisms of GLTSCR2 in hypoxic cell death by means of subtractive hybridization, RT-PCR, Western blot, immunocytochemistry, cell death assay, transient gene overexpression, and determination of mitochondrial membrane potential.
RESULTS
We found that GLTSCR2 was transcriptionally suppressed by hypoxia, and ectopic expression of GLTSCR2 sensitized cells to hypoxic injury. Interestingly, while the majority of hypoxia-inducible pro-death proteins signal through mitochondrion-dependent pathways, GLTSCR2-overexpressed cells underwent apoptosis in a mitochondrion- and caspase-independent manner.
CONCLUSION
Our data categorizes GLTSCR2 as a proapoptotic protein sensitizing cells to hypoxic injury when overexpressed.
目的
我们试图鉴定可诱导缺氧细胞死亡的新基因，以更好地理解缺氧诱导细胞死亡的分子机制。在此过程中发现了GLTSCR2基因。本研究旨在探讨GLTSCR2在缺氧细胞死亡途径中的作用。
方法
本研究通过消减杂交、逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹法、免疫细胞化学、细胞死亡检测、瞬时基因过表达以及线粒体膜电位测定等方法，着重研究GLTSCR2在缺氧细胞死亡中的作用及机制。
结果
我们发现缺氧可转录抑制GLTSCR2，GLTSCR2的异位表达使细胞对缺氧损伤敏感。有趣的是，虽然大多数缺氧诱导的促死亡蛋白通过线粒体依赖途径发出信号，但过表达GLTSCR2的细胞以不依赖线粒体和半胱天冬酶的方式发生凋亡。
结论
我们的数据表明，GLTSCR2是一种促凋亡蛋白，过表达时可使细胞对缺氧损伤敏感。
Zotero 插件