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Diallyl trisulfide protects against high glucose-induced cardiac apoptosis by stimulating the production of cystathionine gamma-lyase-derived hydrogen sulfide.
Int J Cardiol 2015; 195:300-10IJ

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.

CONCLUSION

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+Show Affiliations

Department of Pediatrics, China Medical University Beigang Hospital, Yunlin, Taiwan; Department of Biological Science & Technology College of Life Sciences, China Medical University, Taichung, Taiwan.Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei, Taiwan; Center for General Education, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan.Department of Biological Science & Technology College of Life Sciences, China Medical University, Taichung, Taiwan.Departments of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.Departments of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.Department of Biological Science & Technology College of Life Sciences, China Medical University, Taichung, Taiwan.Health Care Center, Chang Gung Memorial Hospital, Taipei, Taiwan.Department of Cardiology, Taipei City Hospital, Zhongxiao Branch, Taipei, Taiwan.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.Department of Biological Science & Technology College of Life Sciences, China Medical University, Taichung, Taiwan. Electronic address: wwkuo@mail.cmu.edu.tw.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26056963

Citation

Tsai, Cheng-Yen, et al. "Diallyl Trisulfide Protects Against High Glucose-induced Cardiac Apoptosis By Stimulating the Production of Cystathionine Gamma-lyase-derived Hydrogen Sulfide." International Journal of Cardiology, vol. 195, 2015, pp. 300-10.
Tsai CY, Wen SY, Shibu MA, et al. Diallyl trisulfide protects against high glucose-induced cardiac apoptosis by stimulating the production of cystathionine gamma-lyase-derived hydrogen sulfide. Int J Cardiol. 2015;195:300-10.
Tsai, C. Y., Wen, S. Y., Shibu, M. A., Yang, Y. C., Peng, H., Wang, B., ... Kuo, W. W. (2015). Diallyl trisulfide protects against high glucose-induced cardiac apoptosis by stimulating the production of cystathionine gamma-lyase-derived hydrogen sulfide. International Journal of Cardiology, 195, pp. 300-10. doi:10.1016/j.ijcard.2015.05.111.
Tsai CY, et al. Diallyl Trisulfide Protects Against High Glucose-induced Cardiac Apoptosis By Stimulating the Production of Cystathionine Gamma-lyase-derived Hydrogen Sulfide. Int J Cardiol. 2015 Sep 15;195:300-10. PubMed PMID: 26056963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diallyl trisulfide protects against high glucose-induced cardiac apoptosis by stimulating the production of cystathionine gamma-lyase-derived hydrogen sulfide. AU - Tsai,Cheng-Yen, AU - Wen,Su-Ying, AU - Shibu,Marthandam Asokan, AU - Yang,Yao-Chih, AU - Peng,Hanjing, AU - Wang,Binghe, AU - Wei,Yu-Min, AU - Chang,Hung-Yu, AU - Lee,Cheng-Yu, AU - Huang,Chih-Yang, AU - Kuo,Wei-Wen, Y1 - 2015/05/20/ PY - 2015/01/09/received PY - 2015/04/24/revised PY - 2015/05/11/accepted PY - 2015/6/10/entrez PY - 2015/6/10/pubmed PY - 2016/3/24/medline KW - Apoptosis KW - Cystathionine gamma-lyase (CSE) KW - Diallyl trisulfide (DATS) KW - High glucose (HG) KW - Hydrogen sulfide (H(2)S) KW - Reactive oxygen species (ROS) SP - 300 EP - 10 JF - International journal of cardiology JO - Int. J. Cardiol. VL - 195 N2 - 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. CONCLUSION: 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. SN - 1874-1754 UR - https://www.unboundmedicine.com/medline/citation/26056963/Diallyl_trisulfide_protects_against_high_glucose_induced_cardiac_apoptosis_by_stimulating_the_production_of_cystathionine_gamma_lyase_derived_hydrogen_sulfide_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0167-5273(15)01174-2 DB - PRIME DP - Unbound Medicine ER -