The role of tissue transglutaminase 2 (TG2) in cardiac myocyte apoptosis under oxidative stress induced by ischemic injury remains unclear. Here, we investigated the effects of TG2 on apoptosis of cardiomyocytes under oxidative stress. Ectopic expression of TG2 increased caspase-3 activity and calcium overload in cardiomyocytes. Expression levels of TG2 were significantly increased in H2O2-treated cardiomyocytes. Caspase-3 activity assay demonstrated its considerable correlation with TG2 expression, which supported that caspase-3 inhibitor inhibited the apoptosis induced by the ectopic overexpression of TG2. In addition, the other apoptotic signals, such as caspase-8, cytochrome c, and Bax, were increased dependent with TG2 expression in H2O2-treated cardiomyocytes. These results indicated that apoptotic signals had a positive correlation with TG2 expression. The decreased expression of phospholipase C (PLC)-δ1 and phospho-PKC in H 2O2-treated cardiomyocytes were rescued by TG2 silencing. Together, our data strongly suggest that oxidative stress up-regulates TG2 expression in cardiomyocytes, leading to apoptosis.
Bibliographical noteFunding Information:
This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2007-313-E00098) and by a faculty research grant of Yonsei University College of Medicine for 2008.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology