title: Exogenous hydrogen sulphide ameliorates diabetic cardiomyopathy in rats by reversing disordered calcium-handling system in sarcoplasmic reticulum.
abstract: OBJECTIVE
  Hydrogen sulphide (H2 S) has been found to be involved in cardiovascular diseases, but the exact mechanism has not been clarified. The purpose of this study was to investigate whether sodium hydrogen sulphide (NaHS), the donor of H2 S, can improve diabetic cardiomyopathy by reversing disordered calcium-handling system in sarcoplasmic reticulum (SR).
  
  
  METHODS
  Sprague Dawley rats were injected with streptozotocin (STZ, 60 mg/kg, i.p.) to build diabetic model. Treatment groups included: aminoguanidine group (AG, 100 mg/kg, p.o.) and NaHS group (5 mg/kg per day, s.c.).
  
  
  RESULTS
  Cardiac dysfunction and myocardial hypertrophy were found in diabetic model (DM) group, along with increased ROS levels and upregulated mRNA and protein expressions of NADPH p22(phox) , endothelin A receptor (ETA ) and protein kinase Cε (PKCε). Expressions of calcium-handling proteins in SR including FK506-binding proteins (FKBP12.6), sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) and calsequestrin 2 (CASQ2) were downregulated in DM group, accompanied by elevated concentration of diastolic free calcium in high glucose-incubated cardiomyocytes, indicating of calcium leak. After treated by NaHS, these abnormalities were attenuated significantly.
  
  
  CONCLUSIONS
  Exogenous H2 S played a protective role in diabetic cardiomyopathy by inhibiting abnormal calcium-handling system in SR and ET-NADPH oxidase-PKCε pathway.
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Medical School of Southeast University, Nanjing, China.
authors.forename: Yu-Si
authors.initials: YS
authors.lastname: Cheng
authors.affiliation: Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China.
authors.forename: De-Zai
authors.initials: DZ
authors.lastname: Dai
authors.affiliation: Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Medical School of Southeast University, Nanjing, China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Zhu
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Medical School of Southeast University, Nanjing, China.
authors.forename: Bi-Cheng
authors.initials: BC
authors.lastname: Liu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin / Q000494:pharmacology; D013440:Sulfides / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013440:Sulfides; D013311:Streptozocin; D002118:Calcium; C033479:sodium sulfide; D006862:Hydrogen Sulfide
keywords: CASQ2; FKBP12.6; NADPH p22phox; SERCA2a; diabetic cardiomyopathy