title: Sulforaphane prevents rat cardiomyocytes from hypoxia/reoxygenation injury in vitro via activating SIRT1 and subsequently inhibiting ER stress.
abstract: OBJECTIVE
  Sulforaphane (SFN), a natural dietary isothiocyanate, is found to exert beneficial effects for cardiovascular diseases. This study aimed to investigate the mechanisms underlying the protective effects of SFN in a model of myocardial hypoxia/reoxygenation (H/R) injury in vitro.
  
  
  METHODS
  Cultured neonatal rat cardiomyocytes pretreated with SFN were subjected to 3-h hypoxia followed by 3-h reoxygenation. Cell viability and apoptosis were detected. Caspase-3 activity and mitochondrial membrane potential (ΔΨm) was measured. The expression of ER stress-related apoptotic proteins were analyzed with Western blot analyses. Silent information regulator 1 (SIRT1) activity was determined with SIRT1 deacetylase fluorometric assay kit.
  
  
  RESULTS
  SFN (0.1-5 μmol/L) dose-dependently improved the viability of cardiomyocytes, diminished apoptotic cells and suppressed caspase-3 activity. Meanwhile, SFN significantly alleviated the damage of ΔΨm and decreased the expression of ER stress-related apoptosis proteins (GRP78, CHOP and caspase-12), elevating the expression of SIRT1 and Bcl-2/Bax ratio in the cardiomyocytes. Co-treatment of the cardiomyocytes with the SIRT1-specific inhibitor Ex-527 (1 μmol/L) blocked the SFN-induced cardioprotective effects.
  
  
  CONCLUSIONS
  SFN prevents cardiomyocytes from H/R injury in vitro most likely via activating SIRT1 pathway and subsequently inhibiting the ER stress-dependent apoptosis.
authors.affiliation: Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Yun-peng
authors.initials: YP
authors.lastname: Li
authors.affiliation: Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Shu-lin
authors.initials: SL
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Rong-ren
authors.initials: RR
authors.lastname: Kuang
authors.affiliation: Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Xian-bao
authors.initials: XB
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Xu-dong
authors.initials: XD
authors.lastname: Song
authors.affiliation: Department of Cardiology, He-nan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Xue-ming
authors.initials: XM
authors.lastname: Cao
authors.affiliation: Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Ping-zhen
authors.initials: PZ
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Li-zi
authors.initials: LZ
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Ai-hua
authors.initials: AH
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D017879:Isothiocyanates / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism*; D013454:Sulfoxides
chemical_list: D002316:Cardiotonic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; C016766:sulforaphane