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

• Published in: Experimental & molecular medicine 2010, 42(9), , pp.639-650
• Main Authors: Cho, Sung-Yup, Lee, Jin-Haeng, Bae, Han-Dong, Jeong, Eui Man, Jang, Gi-Yong, Kim, Chai-Wan, Shin, Dong-Myung, Jeon, Ju-Hong, Kim, In-Gyu
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Medical Biochemistry; Molecular Medicine; Original; Stem Cells; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.3858/emm.2010.42.9.063

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.