title: Hydrogen Sulfide Protects Cardiomyocytes against Apoptosis in Ischemia/Reperfusion through MiR-1-Regulated Histone Deacetylase 4 Pathway.
abstract: OBJECTIVE
  Hydrogen sulfide (H<Sub>2</Sub>S) is a powerful inhibitor of cardiomyocytes apoptosis following ischemia/reperfusion (IR) injury, but the underlying mechanism remains unclear. Our previous study showed that microRNA-1 (miR-1) was upregulated by 2.21 fold in the IR group compared with that in the H<Sub>2</Sub>S preconditioned group. MiR-206 affected the process of cardiomyocytes hypertrophy by regulating histone deacetylase 4 (HDAC4). HDAC4 is also known to play an anti-apoptotic role in tumor cells, but its role in the myocardium has not been reported. The aim of this study was to test whether H<Sub>2</Sub>S could inhibit apoptosis of cardiomyocytes through HDAC4 regulation by miR-1 in IR.
  
  
  METHODS
  Cardiomyocytes of neonatal rats were subjected to hypoxia/reoxygenation (HR) injury with or without H<Sub>2</Sub>S pretreatment to simulate IR injury Cardiomyocytes were transfected with miR-1 mimic or HDAC4 siRNA to evaluate whether the miR-1-HDAC4 signaling pathway was involved in the protective effect of H<Sub>2</Sub>S.
  
  
  RESULTS
  HR increased cell apoptosis and caspase-3 cleavage, upregulated miR-1, and downregulated HDAC4. H<Sub>2</Sub>S preconditioning attenuated the apoptosis of cardiomyocytes, caspase-3 cleavage and LDH release, and enhanced cell viability In addition, H<Sub>2</Sub>S downregulated miR-1, and preserved HDAC4 expression. HDAC4 protein was down-regulated by miR-1 mimic. Transfection of cardiomyocytes with miR-1 mimic partially reduced the protective effect of H<Sub>2</Sub>S. Meanwhile, transfection of cardiomyocytes with siRNA to HDAC4 partially abrogated the protective effect of H<Sub>2</Sub>S.
  
  
  CONCLUSIONS
  The miR-1-HDAC4 signaling pathway is involved in the protective effect of H<Sub>2</Sub>S against the apoptosis of cardiomyocytes during the IR injury process.
authors.forename: Bo
authors.initials: B
authors.lastname: Kang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Wang
authors.initials: W
authors.lastname: Xi
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Yi
authors.forename: Yundan
authors.initials: Y
authors.lastname: Ciren
authors.forename: Hua
authors.initials: H
authors.lastname: Shen
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Huan
authors.initials: H
authors.lastname: Jiang
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.forename: Zhinong
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D000070416:Antagomirs / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000070416:Antagomirs; C542191:MIRN1 microRNA, rat; D035683:MicroRNAs; D020011:Protective Agents; D034741:RNA, Small Interfering; D053148:Caspase 3; C559944:HDAC4 protein, rat; D006655:Histone Deacetylases; D010100:Oxygen; D006862:Hydrogen Sulfide
keywords: Apoptosis; HDAC4; Hydrogen sulfide; Ischemia-reperfusion injury; MicroRNA-1