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, 168 (1), 270-80

Diallyl Trisufide (DATS) Suppresses High Glucose-Induced Cardiomyocyte Apoptosis by Inhibiting JNK/NFκB Signaling via Attenuating ROS Generation

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Diallyl Trisufide (DATS) Suppresses High Glucose-Induced Cardiomyocyte Apoptosis by Inhibiting JNK/NFκB Signaling via Attenuating ROS Generation

Wei-Wen Kuo et al. Int J Cardiol.

Abstract

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.

Keywords: 2′,7′-Dichlorofluorescein diacetate; 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium-bromide; Apoptosis; Cardiomyocytes; DADS; DAS; DATS; DCF; DCFH-DA; DM; DTT; Diallyl trisulfide (DATS); EMSA; HDAC-1; HG; Hyperglycemia; IκB; IκK; JNK; MAPKs; MI-R; MTT; N-acetyl cysteine; NAC; NADPH; NF-κB; NG; Nuclear factor-κB (NF-κB); ROS; Reactive oxygen species (ROS); SAPKs; STZ; TUNEL; c-Jun N-terminal kinase; diabetes mellitus; diallyl disulfide; diallyl sulfide; diallyl trisulfide; dichlorofluorescein; dithiothreitol; electrophoretic mobility shift assay; high glucose; histone deacetylase-1; inhibitor IκB kinase; inhibitor κ B; mitogen-activated protein-kinases; myocardial ischemia–reperfusion; nicotinamide adenine dinucleotide phosphate; normal glucose; nuclear factor-κB; reactive oxygen species; streptozotocin; stress-activated protein kinases; terminal deoxynucleotide transferase-mediated dUTP nick end labeling.

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