Endothelial CaMKII as a regulator of eNOS activity and NO-mediated vasoreactivity
| العنوان: | Endothelial CaMKII as a regulator of eNOS activity and NO-mediated vasoreactivity |
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| المؤلفون: | Chantal Allamargot, Kim Broadhurst, Isabella M. Grumbach, Velarchana Santhana, Daniel W. Nuno, William J. Kutschke, Kaikobad Irani, Jason A. Scott, Santosh Kumar, Shubha Murthy, Kathryn G. Lamping, Olha M. Koval, Linda J. Zhu, Juan M. Ramiro Diaz |
| المصدر: | PLoS ONE PLoS ONE, Vol 12, Iss 10, p e0186311 (2017) |
| بيانات النشر: | Public Library of Science (PLoS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Adenoviruses, lcsh:Medicine, Blood Pressure, Vasodilation, Pathology and Laboratory Medicine, Biochemistry, Vascular Medicine, environment and public health, Epithelium, chemistry.chemical_compound, Animal Cells, Enos, Medicine and Health Sciences, Post-Translational Modification, Phosphorylation, lcsh:Science, Aorta, Multidisciplinary, biology, Kinase, Chemistry, musculoskeletal, neural, and ocular physiology, Neurochemistry, Animal Models, Cell biology, medicine.anatomical_structure, Experimental Organism Systems, Medical Microbiology, Viral Pathogens, Viruses, cardiovascular system, Neurochemicals, Anatomy, Pathogens, Cellular Types, Research Article, Nitric Oxide Synthase Type III, Endothelium, Bradykinin, Mouse Models, Nitric Oxide, Research and Analysis Methods, Microbiology, Cell Line, Nitric oxide, 03 medical and health sciences, Model Organisms, Ca2+/calmodulin-dependent protein kinase, medicine, Animals, Humans, Microbial Pathogens, lcsh:R, Organisms, Biology and Life Sciences, Endothelial Cells, Proteins, Epithelial Cells, Cell Biology, biology.organism_classification, enzymes and coenzymes (carbohydrates), Biological Tissue, 030104 developmental biology, nervous system, Cardiovascular Anatomy, Blood Vessels, lcsh:Q, DNA viruses, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Neuroscience |
| الوصف: | The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase important in transducing intracellular Ca2+ signals. While in vitro data regarding the role of CaMKII in the regulation of endothelial nitric oxide synthase (eNOS) are contradictory, its role in endothelial function in vivo remains unknown. Using two novel transgenic models to express CaMKII inhibitor peptides selectively in endothelium, we examined the effect of CaMKII on eNOS activation, NO production, vasomotor tone and blood pressure. Under baseline conditions, CaMKII activation was low in the aortic wall. Consistently, systolic and diastolic blood pressure, heart rate and plasma NO levels were unaltered by endothelial CaMKII inhibition. Moreover, endothelial CaMKII inhibition had no significant effect on NO-dependent vasodilation. These results were confirmed in studies of aortic rings transduced with adenovirus expressing a CaMKII inhibitor peptide. In cultured endothelial cells, bradykinin treatment produced the anticipated rapid influx of Ca2+ and transient CaMKII and eNOS activation, whereas CaMKII inhibition blocked eNOS phosphorylation on Ser-1179 and dephosphorylation at Thr-497. Ca2+/CaM binding to eNOS and resultant NO production in vitro were decreased under CaMKII inhibition. Our results demonstrate that CaMKII plays an important role in transient bradykinin-driven eNOS activation in vitro, but does not regulate NO production, vasorelaxation or blood pressure in vivo under baseline conditions. |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::87674b200574ce4c867f6f464a092763 https://doi.org/10.1371/journal.pone.0186311 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....87674b200574ce4c867f6f464a092763 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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