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

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

Research output: Contribution to journalArticle

38 Scopus citations

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. Transglu-taminase 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, over expression 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.

Original languageEnglish (US)
Pages (from-to)639-650
Number of pages12
JournalExperimental and Molecular Medicine
Volume42
Issue number9
DOIs
Publication statusPublished - Sep 30 2010

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Keywords

  • Apoptosis
  • Bax
  • Calcium
  • Mitochondria
  • Transglutaminase 2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry

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