Transglutaminase 2 inhibits apoptosis induced by calciumoverload through down-regulation of Bax.
10.3858/emm.2010.42.9.063
- Author:
Sung Yup CHO
1
;
Jin Haeng LEE
;
Han Dong BAE
;
Eui Man JEONG
;
Gi Yong JANG
;
Chai Wan KIM
;
Dong Myung SHIN
;
Ju Hong JEON
;
In Gyu KIM
Author Information
1. Department of Biochemistry and Molecular Biology/Aging and Apoptosis Research Center (AARC), Seoul National University College of Medicine, Seoul 110-799, Korea. igkim@plaza.snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
Bax;
calcium;
mitochondria;
transglutaminase 2
- MeSH:
*Apoptosis;
Apoptosis Regulatory Proteins/metabolism;
Calcimycin/pharmacology;
Calcium/*metabolism;
Caspases/metabolism;
Cell Death;
Cell Survival;
Cytochromes c/metabolism;
Down-Regulation;
GTP-Binding Proteins/*metabolism;
HEK293 Cells;
Hela Cells;
Humans;
Ionophores/pharmacology;
Mitochondria/metabolism;
Transglutaminases/*metabolism;
bcl-2-Associated X Protein/genetics/*metabolism
- From:Experimental & Molecular Medicine
2010;42(9):639-650
- CountryRepublic of Korea
- Language:English
-
Abstract:
An abrupt increase of intracellular Ca2+ is observed in cells under hypoxic or oxidatively stressed conditions. The dysregulated increase of cytosolic Ca2+ triggers apoptotic cell death through mitochondrial swelling and activation of Ca2+-dependent enzymes. Transglutaminase 2 (TG2) is a Ca2+-dependent enzyme that catalyzes transamidation reaction producing cross-linked and polyaminated proteins. TG2 activity is known to be involved in the apoptotic process. However, the pro-apoptotic role of TG2 is still controversial. In this study, we investigate the role of TG2 in apoptosis induced by Ca2+-overload. Overexpression of TG2 inhibited the A23187-induced apoptosis through suppression of caspase-3 and -9 activities, cytochrome c release into cytosol, and mitochondria membrane depolarization. Conversely, down-regulation of TG2 caused the increases of cell death, caspase-3 activity and cytochrome c in cytosol in response to Ca2+-overload. Western blot analysis of Bcl-2 family proteins showed that TG2 reduced the expression level of Bax protein. Moreover, overexpression of Bax abrogated the anti-apoptotic effect of TG2, indicating that TG2-mediated suppression of Bax is responsible for inhibiting cell death under Ca2+-overloaded conditions. Our findings revealed a novel anti-apoptotic pathway involving TG2, and suggested the induction of TG2 as a novel strategy for promoting cell survival in diseases such as ischemia and neurodegeneration.
