NADPH oxidase-derived superoxide anion-induced apoptosis is inhibited by diallyl trisufide (DATS) in cardiomyocytes exposed to high glucose
Wei-Wen Kuo
Department of Biological Science and Technology, China Medical University 404, Taichung Taiwan, Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan
Abstract:
Hyperglycemia can induce reactive oxygen species (ROS), leading to cardiomyocyte apoptosis and cardiac dysfunction. In our previous study, we show that NADPH oxidase-derived ROS induces JNK signaling to enhance nuclear factor-?B (NF-?B) nuclear activation, contributing to high glucose-triggered cardiomyocyte apoptosis. In this study, we investigate the mechanism of antiapoptosis by diallyl trisulfide (DATS) on high-glucose treated H9c2 cells. H9c2 cells were treated with media containing 5.5 or 33 mM of glucose for 36hr with presence or absence of DATS. Our data demonstrated that increased levels of ROS measured by flow cytometry, p22, phosphorylated IkB and c-Jun detected by western blot were dose-dependently decreased after the treatment of DATS in H9c2 cells exposed to high glucose. The results of activated caspase 3 levels and TUNEL assay showed a significant decrease of cell death by DATS. The results of nuclear translocation detected by immunofluresence assay, promoter sequence binding ability estimated by EMSA, transcription activity evaluated by luciferase assay and downstream gene, COX, expressions examined by RT-PCR indicated that increased NF-?B nuclear activation by high glucose exposure were decreased by the treatment of DATS in H9c2 cells. Therefore, we elucidated the roles of the DATS on inhibiting high glucose induced cardiomyocyte apoptosis is mediated through inhibiting NADPH oxidase-derived ROS and its downstream JNK/NFkB signalings.
