© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Signal transduction of eNOS activation
Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany
* Corresponding author. Tel.: +49-69-63016052; fax: +49-60-63017668 Fleming{at}em.uni-frankfurt.de
Consistent with its classification as a Ca2+/calmodulin-dependent enzyme the constitutive endothelial nitric oxide (NO) synthase (eNOS) can be activated by receptor-dependent and -independent agonists as a consequence of an increase in the intracellular concentration of free Ca2+ ([Ca2+]i) and the association of the Ca2+/calmodulin complex with eNOS. Additional post-translational mechanisms regulate the activity of eNOS, including the interaction of eNOS with caveolin-1, heat shock protein 90 (Hsp90), or membrane phospholipids, as well as enzyme translocation and phosphorylation. In response to fluid shear stress the maintained production of NO by native and cultured endothelial cells is associated with only a transient increase in [Ca2+]i. In the absence of extracellular Ca2+ and in the presence of calmodulin antagonists, shear stress stimulates a maintained production of NO which is insensitive to the removal of extracellular Ca2+, but sensitive to tyrosine kinase inhibitors, Hsp90-binding proteins and phosphatidylinositol 3-kinase inhibitors. A pharmacologically identical activation of eNOS can be induced by protein tyrosine phosphatase inhibitors suggesting that the phosphorylation of eNOS, and possibly that of an associated regulatory protein(s), is crucial for its Ca2+-independent activation.
KEYWORDS Endothelial function; Nitric oxide; Signal transduction
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Asai, K. Takeuchi, M. Saotome, T. Urushida, H. Katoh, H. Satoh, H. Hayashi, and H. Watanabe Extracellular acidosis suppresses endothelial function by inhibiting store-operated Ca2+ entry via non-selective cation channels Cardiovasc Res, July 1, 2009; 83(1): 97 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Sud, S. Kumar, S. Wedgwood, and S. M. Black Modulation of PKC{delta} signaling alters the shear stress-mediated increases in endothelial nitric oxide synthase transcription: role of STAT3 Am J Physiol Lung Cell Mol Physiol, March 1, 2009; 296(3): L519 - L526. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Nacci, M. Tarquinio, L. De Benedictis, A. Mauro, A. Zigrino, M. R. Carratu, M. J. Quon, and M. Montagnani Endothelial Dysfunction in Mice with Streptozotocin-induced Type 1 Diabetes Is Opposed by Compensatory Overexpression of Cyclooxygenase-2 in the Vasculature Endocrinology, February 1, 2009; 150(2): 849 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Du and A. F. Chen A New Role for Caveolin-1: Regulation of Guanosine Triphosphate Cyclohydrolase I and Tetrahydrobiopterin in Endothelial Cells Hypertension, February 1, 2009; 53(2): 115 - 117. [Full Text] [PDF]
|
|
|
|
 |
|
 H.-C. Chang, T.-L. Chen, and R.-M. Chen Cytoskeleton Interruption in Human Hepatoma HepG2 Cells Induced by Ketamine Occurs Possibly through Suppression of Calcium Mobilization and Mitochondrial Function Drug Metab. Dispos., January 1, 2009; 37(1): 24 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Averna, R. Stifanese, R. De Tullio, M. Passalacqua, F. Salamino, S. Pontremoli, and E. Melloni Functional Role of HSP90 Complexes with Endothelial Nitric-oxide Synthase (eNOS) and Calpain on Nitric Oxide Generation in Endothelial Cells J. Biol. Chem., October 24, 2008; 283(43): 29069 - 29076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Chen, M. Bacanamwo, and D. G. Harrison Activation of p300 Histone Acetyltransferase Activity Is an Early Endothelial Response to Laminar Shear Stress and Is Essential for Stimulation of Endothelial Nitric-oxide Synthase mRNA Transcription J. Biol. Chem., June 13, 2008; 283(24): 16293 - 16298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Belmonte and M. Morad 'Pressure-flow'-triggered intracellular Ca2+ transients in rat cardiac myocytes: possible mechanisms and role of mitochondria J. Physiol., March 1, 2008; 586(5): 1379 - 1397. [Abstract] [Full Text] [PDF]
|
|