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

Abstract

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.

• Authors: Ji-Hye Yim, Yong-Jun Kim, Young-Eun Cho, Jeong-Hun Ko, Su-Mi Kim, Jee-Youn Kim, Jae-Hoon Park
• Journal: Pathobiology : journal of immunopathology, molecular and cellular biology (Pathobiology) Vol. 74 Issue 5 Pg. 301-8 ( 2007) ISSN: 1423-0291 [Electronic] Switzerland
• PMID: 17890897 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2007 S. Karger AG, Basel.

Chemical References

• NOP53 protein, human
• Tumor Suppressor Proteins

Topics

• Apoptosis (physiology)
• Blotting, Western
• Cell Hypoxia (genetics)
• Cell Line
• Gene Expression
• Humans
• Immunohistochemistry
• Membrane Potential, Mitochondrial (physiology)
• Mitochondria (pathology)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (physiology)
• Tumor Suppressor Proteins (genetics, metabolism)