Neuronostatin Attenuates Myocardial Contractile Function through Inhibition of Sarcoplasmic Reticulum Ca2+-ATPase in Murine Heart

Cellular Physiology and Biochemistry

关键词: Neuronostatin;    Cardiac;    Contractile;    SERCA;    AMPK;   

DOI  :  10.1159/000362969

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND