Neuronostatin Attenuates Myocardial Contractile Function through Inhibition of Sarcoplasmic Reticulum Ca2+-ATPase in Murine Heart
العنوان: | Neuronostatin Attenuates Myocardial Contractile Function through Inhibition of Sarcoplasmic Reticulum Ca2+-ATPase in Murine Heart |
---|---|
المؤلفون: | Nan Hu, Xihui Xu, Hailong Dong, Xiyao Chen, Yinan Hua, Xiaoling Zhu, Sreejayan Nair, Jun Ren, Willis K. Samson, Fuling Luo, Miao-Zhang Zhu, Lize Xiong |
المصدر: | Cellular Physiology and Biochemistry, Vol 33, Iss 6, Pp 1921-1932 (2014) |
بيانات النشر: | Cell Physiol Biochem Press GmbH & Co KG, 2014. |
سنة النشر: | 2014 |
مصطلحات موضوعية: | Male, Cardiac function curve, AMPK, medicine.medical_specialty, SERCA, MAP Kinase Signaling System, Physiology, Peptide Hormones, Neuronostatin, Blotting, Western, Contractile, AMP-Activated Protein Kinases, Biology, lcsh:Physiology, Sarcoplasmic Reticulum Calcium-Transporting ATPases, lcsh:Biochemistry, Mice, Downregulation and upregulation, Internal medicine, medicine, Animals, Myocytes, Cardiac, lcsh:QD415-436, Phosphorylation, Cell Shape, Cells, Cultured, Cell Size, lcsh:QP1-981, Myocardium, Endoplasmic reticulum, Heart, Myocardial Contraction, Phospholamban, Mice, Inbred C57BL, Endocrinology, Echocardiography, Calcium, Proto-Oncogene Proteins c-akt, Cardiac, Injections, Intraperitoneal, Intracellular, Homeostasis |
الوصف: | 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. |
اللغة: | English |
تدمد: | 1421-9778 1015-8987 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a6155163736624f0d1588101c98bed57 http://www.karger.com/Article/FullText/362969 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....a6155163736624f0d1588101c98bed57 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 14219778 10158987 |
---|