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Transglutaminase 2 inhibits apoptosis induced by calcium-overload through down-regulation of Bax

Cited 42 time in Web of Science Cited 44 time in Scopus
Authors

Cho, Sung-Yup; Lee, Jin-Haeng; Bae, Han-Dong; Jeong, Eui Man; Jeon, Ju-Hong; Kim, In-Gyu; Shin, Dong-Myung; Kim, Chai-Wan; Jang, Gi-Yong

Issue Date
2010-09-30
Publisher
KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY
Citation
EXPERIMENTAL AND MOLECULAR MEDICINE; Vol.42 9; 639-650
Keywords
apoptosisBaxcalciumtransglutaminase 2mitochondria
Abstract
An abrupt increase of intracellular Ca(2+) is observed in cells under hypoxic or oxidatively stressed conditions. The dysregulated increase of cytosolic Ca(2+) triggers apoptotic cell death through mitochondrial swelling and activation of Ca(2+)-dependent enzymes. Transglutaminase 2 (TG2) is a Ca(2+)-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 Ca(2+)-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 Ca(2+)-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 Ca(2+)-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.
ISSN
1226-3613
Language
English
URI
https://hdl.handle.net/10371/76214
DOI
https://doi.org/10.3858/emm.2010.42.9.063
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