دورية أكاديمية
Vasoinhibins Prevent Bradykinin-Stimulated Endothelial Cell Proliferation by Inactivating eNOS via Reduction of both Intracellular Ca2+ Levels and eNOS Phosphorylation at Ser1179
| العنوان: | Vasoinhibins Prevent Bradykinin-Stimulated Endothelial Cell Proliferation by Inactivating eNOS via Reduction of both Intracellular Ca2+ Levels and eNOS Phosphorylation at Ser1179 |
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| المؤلفون: | Carmen Clapp, Stéphanie Thebault, Gonzalo Martínez De la Escalera, Fernando López-Casillas, Luis Vaca, David Arredondo Zamarripa, Gabriel Nava, Celina García, Carmen González |
| المصدر: | Pharmaceuticals, Vol 4, Iss 7, Pp 1052-1069 (2011) |
| بيانات النشر: | MDPI AG, 2011. |
| سنة النشر: | 2011 |
| المجموعة: | LCC:Medicine LCC:Pharmacy and materia medica |
| مصطلحات موضوعية: | vasoinhibins, 16kDa-prolactin, bradykinin, endothelial nitric oxide synthase, calcium mobilization, transient receptor potential channels, Medicine, Pharmacy and materia medica, RS1-441 |
| الوصف: | Vasoinhibins, a family of antiangiogenic peptides derived from prolactin proteolysis, inhibit the vascular effects of several proangiogenic factors, including bradykinin (BK). Here, we report that vasoinhibins block the BK-induced proliferation of bovine umbilical vein endothelial cells. This effect is mediated by the inactivation of endothelial nitric oxide synthase (eNOS), as the NO donor DETA-NONOate reverted vasoinhibin action. It is an experimentally proven fact that the elevation of intracellular Ca2+ levels ([Ca2+]i) upon BK stimulation activates eNOS, and vasoinhibins blocked the BK-mediated activation of phospholipase C and the formation of inositol 1,4,5-triphosphate leading to a reduced release of Ca2+ from intracellular stores. The [Ca2+]i rise evoked by BK also involves the influx of extracellular Ca2+ via canonical transient receptor potential (TRPC) channels. Vasoinhibins likely interfere with TRPC-mediated Ca2+ entry since La3+, which is an enhancer of TRPC4 and TRPC5 channel activity, prevented vasoinhibins from blocking the stimulation by BK of endothelial cell NO production and proliferation, and vasoinhibins reduced the BK-induced increase of TRPC5 mRNA expression. Finally, vasoinhibins prevented the BK-induced phosphorylation of eNOS at Ser1179, a post-translational modification that facilitates Ca2+-calmodulin activation of eNOS. Together, our data show that vasoinhibins, by lowering NO production through the inhibition of both [Ca2+]i mobilization and eNOS phosphorylation, prevent the BK-induced stimulation of endothelial cell proliferation. Thus, vasoinhibins help to regulate BK effects on angiogenesis and vascular homeostasis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1424-8247 |
| العلاقة: | http://www.mdpi.com/1424-8247/4/7/1052Test/; https://doaj.org/toc/1424-8247Test |
| DOI: | 10.3390/ph4071052 |
| الوصول الحر: | https://doaj.org/article/559022d0b1704bbca5bdfa11c8ee9dbdTest |
| رقم الانضمام: | edsdoj.559022d0b1704bbca5bdfa11c8ee9dbd |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14248247 |
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| DOI: | 10.3390/ph4071052 |