title: Diallyl trisulfide protects against high glucose-induced cardiac apoptosis by stimulating the production of cystathionine gamma-lyase-derived hydrogen sulfide.
abstract: BACKGROUND
  Cystathionine-γ-lyase (CSE)-derived hydrogen sulfide (H2S) is a potent cardioprotective agent. We investigated the effects of diallyl trisulfide (DATS) on CSE expression and H2S generation in myocardium and examined whether DATS-mediated H2S generation effectively protects rat heart from diabetes-induced cardiac damage.
  
  
  METHODS
  The correlations between the effects of hyperglycemia and diabetes on CSE expression and the effects of DATS and H2S on hyperglycemia and diabetes were examined in vitro in the cardiomyocyte cell line H9c2 and in vivo in hearts from rats with streptozotocin-induced diabetes mellitus (DM).
  
  
  RESULTS
  Expression of CSE, a catalyst of H2S production, was suppressed in H9c2 cells treated with high glucose (33 mM) and in DM rat hearts. CSE suppression also correlated with a decrease in the activation of the pro-survival protein kinase Akt. Treatment of H9c2 cells with DATS resulted in increased CSE expression and a reduction in apoptosis via a mechanism involving IGF1R/pAkt signaling and by modulating the expression of reactive oxygen species-related enzymes. The role CSE plays in the cardioprotective effects of DATS was further confirmed by CSE inhibition assays including inhibitors and siRNA.
  
  
  CONCLUSIONS
  DATS produces H2S as efficiently as NaSH and DATS-derived H2S provides effective cardioprotection. Further, our data indicate that H2S plays a major role in the protective effect of DATS against apoptosis of cardiomyocytes.
authors.affiliation: Department of Pediatrics, China Medical University Beigang Hospital, Yunlin, Taiwan; Department of Biological Science & Technology College of Life Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei, Taiwan; Center for General Education, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Wen
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan.
authors.forename: Marthandam Asokan
authors.initials: MA
authors.lastname: Shibu
authors.affiliation: Department of Biological Science & Technology College of Life Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Yao-Chih
authors.initials: YC
authors.lastname: Yang
authors.affiliation: Departments of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Hanjing
authors.initials: H
authors.lastname: Peng
authors.affiliation: Departments of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Binghe
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Biological Science & Technology College of Life Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Wei
authors.affiliation: Health Care Center, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Hung-Yu
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Department of Cardiology, Taipei City Hospital, Zhongxiao Branch, Taipei, Taiwan.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan; Department of Chinese Medicine, China Medical University Hospital, Taichung 404, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung 413, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Biological Science & Technology College of Life Sciences, China Medical University, Taichung, Taiwan. Electronic address: wwkuo@mail.cmu.edu.tw.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D002460:Cell Line; D003542:Cystathionine gamma-Lyase / Q000378:metabolism*; D019610:Cytoprotection; D048909:Diabetes Complications / Q000378:metabolism*; D004195:Disease Models, Animal; D005737:Garlic; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides / Q000494:pharmacology*
chemical_list: D000498:Allyl Compounds; D002316:Cardiotonic Agents; D013440:Sulfides; C042577:diallyl trisulfide; D003542:Cystathionine gamma-Lyase; D005947:Glucose; D006862:Hydrogen Sulfide
keywords: Apoptosis; Cystathionine gamma-lyase (CSE); Diallyl trisulfide (DATS); High glucose (HG); Hydrogen sulfide (H(2)S); Reactive oxygen species (ROS)