title: Neuronostatin attenuates myocardial contractile function through inhibition of sarcoplasmic reticulum Ca2+-ATPase in murine heart.
abstract: OBJECTIVE
  Neuronostatin, derived from the somatostatin preprohormone, was recently identified to be produced by several tissues exerting a role in cardiovascular regulation and metabolism. Nonetheless, the precise mechanism behind neuronostatin-elicited myocardial responses remains elusive.
  
  
  METHODS
  This study was designed to elucidate the impact of neuronostatin on cardiac contractile function and the underlying mechanism of action involved. Adult male C57 BL/6 mice were subjected to a bolus injection of neuronostatin (50 μg/kg, i.p.). Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ handling properties were monitored to evaluate the effect of neuronostatin on cardiac function. Western blot analysis was used to examine potential signaling mechanisms involved.
  
  
  RESULTS
  Neuronostatin administration suppressed myocardial and cardiomyocyte contractile function and disturbed intracellular Ca2+ homeostasis. We observed enlarged LVESD (with unchanged LVEDD), reduced fractional shortening, depressed peak shortening, maximal velocity of shortening/relengthening, resting and electrically-stimulated rise in intracellular Ca2+, and prolonged relengthening duration in hearts from neuronostatin-treated mice. These effects were accompanied by downregulation of phosphorylation of sarcoplasmic reticulum Ca2+- ATPase (SERCA) and phospholamban (PLB) and activation of AMPK.
  
  
  CONCLUSIONS
  Our data suggest that the cardiac depressant properties of neuronostatin possibly associated with loss of SERCA phosphorylation and AMPK activation. These findings revealed a potent inhibitory capacity for neuronostatin on cardiac function, the physiological relevance of which deserves further study.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhu
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Xiyao
authors.initials: X
authors.lastname: Chen
authors.forename: Miao-Zhang
authors.initials: MZ
authors.lastname: Zhu
authors.forename: Hailong
authors.initials: H
authors.lastname: Dong
authors.forename: Xihui
authors.initials: X
authors.lastname: Xu
authors.forename: Fuling
authors.initials: F
authors.lastname: Luo
authors.forename: Yinan
authors.initials: Y
authors.lastname: Hua
authors.forename: Sreejayan
authors.initials: S
authors.lastname: Nair
authors.forename: Willis K
authors.initials: WK
authors.lastname: Samson
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004452:Echocardiography; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007274:Injections, Intraperitoneal; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D036361:Peptide Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D036361:Peptide Hormones; C543371:neuronostatin, mouse; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium