NADPH oxidase-derived superoxide anion-induced apoptosis is mediated via the JNK-dependent activation of NF-κB in cardiomyocytes exposed to high glucose.

Hyperglycemia-induced generation of reactive oxygen species (ROS) can lead to cardiomyocyte apoptosis and cardiac dysfunction. However, the mechanism by which high glucose causes cardiomyocyte apoptosis is not clear. In this study, we investigated the signaling pathways involved in NADPH oxidase-derived ROS-induced apoptosis in cardiomyocytes under hyperglycemic conditions. H9c2 cells were treated with 5.5 or 33 mM glucose for 36 h. We found that 33 mM glucose resulted in a time-dependent increase in ROS generation as well as a time-dependent increase in protein expression of p22(phox), p47(phox), gp91(phox), phosphorylated IκB, c-Jun N-terminal kinase (JNK) and p38, as well as the nuclear translocation of NF-kB. Treatment with apocynin or diphenylene iodonium (DPI), NADPH oxidase inhibitors, resulted in reduced expression of p22(phox), p47(phox), gp91(phox), phosphorylated IκB, c-Jun N-terminal kinase (JNK) and p38. In addition, treatment with JNK and NF-kB siRNAs blocked the activity of caspase-3. Furthermore, treatment with JNK, but not p38, siRNA inhibited the glucose-induced activation of NF-κB. Similar results were obtained in neonatal cardiomyocytes exposed to high glucose concentrations. Therefore, we propose that NADPH oxidase-derived ROS-induced apoptosis is mediated via the JNK-dependent activation of NF-κB in cardiomyocytes exposed to high glucose.

Tsai KH ，Wang WJ ，Lin CW ，Pai P ，Lai TY ，Tsai CY ，Kuo WW ... -  《-》

Diallyl trisufide (DATS) suppresses high glucose-induced cardiomyocyte apoptosis by inhibiting JNK/NFκB signaling via attenuating ROS generation.

Hyperglycemia is an important risk factor for cardiovascular diseases no matter if it resulted from type I or type II diabetes mellitus. High glucose-induced generation of reactive oxygen species (ROS) can lead to diabetic cardiomyopathy. In our previous study, we showed that NADPH oxidase-related ROS-induced apoptosis is mediated via the JNK-dependent activation of NF-κB in cardiomyocytes exposed to high glucose (HG). In this study, we investigated the mechanisms governing the anti-apoptotic effect of diallyl trisulfide (DATS) on HG-exposed cardiac cells both in vitro and in vivo. H9c2 cells were incubated with media containing 5.5 or 33 mM of glucose for 36 h in the presence or absence of DATS. We found that DATS treatment led to a dose-dependent decrease in ROS levels as well as protein levels of p22phox, gp91phox, phosphorylated JNK, and phosphorylated c-Jun. In addition, DATS inhibited the HG-induced activation of caspase 3 as well as the nuclear translocation of NF-κB. Similar results were observed in HG-exposed neonatal primary cardiomyocytes and streptozotocin-treated diabetic rats. Echocardiographic data showed that DATS administration led to a marked increase in fractional shortening and cardiac output. DATS appears to suppress high glucose-induced cardiomyocyte apoptosis by inhibiting NADPH oxidase-related ROS and its downstream JNK/NF-κB signaling, and may possess the potential on the therapy of diabetic cardiomyopathy.

Kuo WW ，Wang WJ ，Tsai CY ，Way CL ，Hsu HH ，Chen LM ... -  《-》

Panaxydol induces apoptosis through an increased intracellular calcium level, activation of JNK and p38 MAPK and NADPH oxidase-dependent generation of reactive oxygen species.

Kim JY ，Yu SJ ，Oh HJ ，Lee JY ，Kim Y ，Sohn J ... -  《-》

Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: role of NF-kappa B, p38 and JNK MAPK pathway.

Ghosh J ，Das J ，Manna P ，Sil PC ... -  《-》

NADPH oxidase is involved in angiotensin II-induced apoptosis in H9C2 cardiac muscle cells: effects of apocynin.

Qin F ，Patel R ，Yan C ，Liu W ... -  《FREE RADICAL BIOLOGY AND MEDICINE》