title: Diallyl trisufide (DATS) suppresses high glucose-induced cardiomyocyte apoptosis by inhibiting JNK/NFκB signaling via attenuating ROS generation.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 40402, Taiwan, ROC. wwkuo@mail.cmu.edu.tw
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.forename: Wei-Jan
authors.initials: WJ
authors.lastname: Wang
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Tsai
authors.forename: Chia-Li
authors.initials: CL
authors.lastname: Way
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Hsu
authors.forename: Li-Mien
authors.initials: LM
authors.lastname: Chen
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000633:toxicity*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013440:Sulfides / Q000494:pharmacology*
chemical_list: D000498:Allyl Compounds; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013440:Sulfides; C042577:diallyl trisulfide; D048031:JNK Mitogen-Activated Protein Kinases; D005947:Glucose