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

作者：Kuo Wei Wen; Wang Wei Jan; Tsai Cheng Yen; Way Chia Li; Hsu Hsi Hsien; Chen Li Mien^*

来源：International Journal of Cardiology, 2013, 168(1): 270-280.

DOI：10.1016/j.ijcard.2012.09.080

• Hyperglycemia
• Cardiomyocytes
• Nuclear factor-kappa B (NF-kappa B)
• Reactive oxygen species (ROS)
• Diallyl trisulfide (DATS)
• Apoptosis

Background: 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-kappa B in cardiomyocytes exposed to high glucose (HG). %26lt;br%26gt;Objective: 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. %26lt;br%26gt;Methods: H9c2 cells were incubated with media containing 5.5 or 33 mM of glucose for 36 h in the presence or absence of DATS. %26lt;br%26gt;Results: 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-kappa B. 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. %26lt;br%26gt;Conclusion: DATS appears to suppress high glucose-induced cardiomyocyte apoptosis by inhibiting NADPH oxidase-related ROS and its downstream JNK/NF-kappa B signaling, and may possess the potential on the therapy of diabetic cardiomyopathy.

• 出版日期2013-9-20
• 单位中国医科大学