Tissue transglutaminase 2 promotes apoptosis of rat neonatal cardiomyocytes under oxidative stress.
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 H(2)O(2)-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 H(2)O(2)-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(2)O(2)-treated cardiomyocytes were rescued by TG2 silencing. Together, our data strongly suggest that oxidative stress up-regulates TG2 expression in cardiomyocytes, leading to apoptosis.
Research Institute of Science for Aging, Yonsei University, Seoul, Korea.
Heesang
H
Song
Byoung-Keuk
BK
Kim
Woochul
W
Chang
Soyeon
S
Lim
Byeong-Wook
BW
Song
Min-Ji
MJ
Cha
Yangsoo
Y
Jang
Ki-Chul
KC
Hwang
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020868:Gene Silencing / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D018384:Oxidative Stress / Q000187:drug effects; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D011503:Transglutaminases / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
C000717609:Tgm2 protein, rat; D006861:Hydrogen Peroxide; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D053148:Caspase 3; D019204:GTP-Binding Proteins