Transglutaminase 2 inhibits apoptosis induced by calciumoverload through down-regulation of Bax
Experimental & Molecular Medicine
;
: 639-650, 2010.
Article
in English
| WPRIM
| ID: wpr-162253
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
HeLa Cells
/
Down-Regulation
/
Cell Survival
/
Transglutaminases
/
Calcium
/
Calcimycin
/
Cell Death
/
Apoptosis
/
GTP-Binding Proteins
/
Caspases
Limits:
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2010
Type:
Article
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