GLTSCR2 sensitizes cells to hypoxic injury without involvement of mitochondrial apoptotic cascades.
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.


CONCLUSIONS
Our data categorizes GLTSCR2 as a proapoptotic protein sensitizing cells to hypoxic injury when overexpressed.
Yim
Ji-Hye
JH
Department of Pathology and Medical Research Center for Bioreaction to Reactive Oxygen Species, College of Medicine, Kyung Hee University, Seoul, Korea.
Kim
Yong-Jun
YJ
Cho
Young-Eun
YE
Ko
Jeong-Hun
JH
Kim
Su-Mi
SM
Kim
Jee-Youn
JY
Park
Jae-Hoon
JH
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000235:genetics*; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
C500712:NOP53 protein, human; D025521:Tumor Suppressor Proteins