Neuronostatin inhibits cardiac contractile function via a protein kinase A- and JNK-dependent mechanism in murine hearts
| العنوان: | Neuronostatin inhibits cardiac contractile function via a protein kinase A- and JNK-dependent mechanism in murine hearts |
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| المؤلفون: | Willis K. Samson, Heng Ma, Jun Ren, Yinan Hua |
| المصدر: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 297:R682-R689 |
| بيانات النشر: | American Physiological Society, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Cell signaling, medicine.medical_specialty, Time Factors, Proto-Oncogene Proteins c-jun, Physiology, Peptide Hormones, Neuropeptide, In Vitro Techniques, Peptide hormone, Biology, Ventricular Function, Left, Immediate early protein, Immediate-Early Proteins, Mice, Heart Rate, Physiology (medical), Internal medicine, Ventricular Pressure, medicine, Animals, Myocytes, Cardiac, RNA, Messenger, Protein kinase A, Protein Kinase Inhibitors, Protein Kinase C, Protein kinase C, JNK Mitogen-Activated Protein Kinases, Articles, Cyclic AMP-Dependent Protein Kinases, Myocardial Contraction, Cell biology, Perfusion, Endocrinology, Somatostatin, Female, Signal transduction, Proto-Oncogene Proteins c-fos, Signal Transduction |
| الوصف: | Neuronostatin, a newly identified peptide hormone sharing the same precursor with somatostatin, exerts multiple pharmacological effects in gastrointestinal tract, hypothalamus, and cerebellum. However, the cardiovascular effect of neuronostatin is unknown. The aim of this study was to elucidate the impact of neuronostatin on cardiac contractile function in murine hearts and isolated cardiomyocytes. Short-term exposure of neuronostatin depressed left ventricular developed pressure (LVDP), maximal velocity of pressure development (±dP/d t), and heart rate in Langendorff heart preparation. Consistently, neuronostatin inhibited peak shortening (PS) and maximal velocity of shortening/relengthening (±dL/d t) without affecting time-to-PS (TPS) and time-to-90% relengthening (TR90) in cardiomyocytes. The neuronostatin-elicited cardiomyocyte mechanical responses were mimicked by somatostatin, the other posttranslational product of preprosomatostatin. Furthermore, the neuronostatin-induced cardiomyocyte mechanical effects were ablated by the PKA inhibitor H89 (1 μM) and the Jun N-terminal kinase (JNK) inhibitor SP600125 (20 μM). The PKC inhibitor chelerythrine (1 μM) failed to alter neuronostatin-induced cardiomyocyte mechanical responses. To the contrary, chelerythrine, but not H89, abrogated somatostatin-induced cardiomyocyte contractile responses. Our results also showed enhanced c-fos and c-jun expression in response to neuronostatin exposure (0.5 to 2 h). Taken together, our data suggest that neuronostatin is a peptide hormone with overt cardiac depressant action. The neuronostatin-elicited cardiac contractile response appears to be mediated, at least in part, through a PKA- and/or JNK-dependent mechanism. |
| تدمد: | 1522-1490 0363-6119 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::98987740d5cab0d4d08b4534a16ceba4 https://doi.org/10.1152/ajpregu.00196.2009 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....98987740d5cab0d4d08b4534a16ceba4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221490 03636119 |
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