Endothelial CaMKII as a regulator of eNOS activity and NO-mediated vasoreactivity

Autor: 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
Rok vydání: 2017
Předmět:
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
Zdroj: PLoS ONE
PLoS ONE, Vol 12, Iss 10, p e0186311 (2017)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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