Neuronostatin attenuates myocardial contractile function through inhibition of sarcoplasmic reticulum Ca2+-ATPase in murine heart

Cell Physiol Biochem. 2014;33(6):1921-32. doi: 10.1159/000362969.


Background/aims: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Blotting, Western
  • Calcium / metabolism
  • Cell Shape / drug effects
  • Cell Size / drug effects
  • Cells, Cultured
  • Echocardiography
  • Heart / drug effects*
  • Heart / physiology
  • Injections, Intraperitoneal
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Contraction / drug effects*
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / physiology
  • Peptide Hormones / administration & dosage
  • Peptide Hormones / pharmacology*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / antagonists & inhibitors*
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism


  • Peptide Hormones
  • neuronostatin, mouse
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinases
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium