TY - JOUR T1 - Diallyl trisufide (DATS) suppresses high glucose-induced cardiomyocyte apoptosis by inhibiting JNK/NFκB signaling via attenuating ROS generation. AU - Kuo,Wei-Wen, AU - Wang,Wei-Jan, AU - Tsai,Cheng-Yen, AU - Way,Chia-Li, AU - Hsu,Hsi-Hsien, AU - Chen,Li-Mien, Y1 - 2012/11/13/ PY - 2011/11/18/received PY - 2012/06/02/revised PY - 2012/09/15/accepted PY - 2012/11/20/entrez PY - 2012/11/20/pubmed PY - 2014/5/7/medline KW - 2′,7′-Dichlorofluorescein diacetate KW - 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium-bromide KW - Apoptosis KW - Cardiomyocytes KW - DADS KW - DAS KW - DATS KW - DCF KW - DCFH-DA KW - DM KW - DTT KW - Diallyl trisulfide (DATS) KW - EMSA KW - HDAC-1 KW - HG KW - Hyperglycemia KW - IκB KW - IκK KW - JNK KW - MAPKs KW - MI-R KW - MTT KW - N-acetyl cysteine KW - NAC KW - NADPH KW - NF-κB KW - NG KW - Nuclear factor-κB (NF-κB) KW - ROS KW - Reactive oxygen species (ROS) KW - SAPKs KW - STZ KW - TUNEL KW - c-Jun N-terminal kinase KW - diabetes mellitus KW - diallyl disulfide KW - diallyl sulfide KW - diallyl trisulfide KW - dichlorofluorescein KW - dithiothreitol KW - electrophoretic mobility shift assay KW - high glucose KW - histone deacetylase-1 KW - inhibitor IκB kinase KW - inhibitor κ B KW - mitogen-activated protein-kinases KW - myocardial ischemia–reperfusion KW - nicotinamide adenine dinucleotide phosphate KW - normal glucose KW - nuclear factor-κB KW - reactive oxygen species KW - streptozotocin KW - stress-activated protein kinases KW - terminal deoxynucleotide transferase-mediated dUTP nick end labeling SP - 270 EP - 80 JF - International journal of cardiology JO - Int. J. Cardiol. VL - 168 IS - 1 N2 - 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-κB in cardiomyocytes exposed to high glucose (HG). 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. 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. 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-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. CONCLUSION: 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. SN - 1874-1754 UR - https://www.unboundmedicine.com/medline/citation/23158927/Diallyl_trisufide__DATS__suppresses_high_glucose_induced_cardiomyocyte_apoptosis_by_inhibiting_JNK/NFκB_signaling_via_attenuating_ROS_generation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0167-5273(12)01186-2 DB - PRIME DP - Unbound Medicine ER -