Molecular mechanisms underlying the activation of eNOS.
Endothelial cells situated at the interface between blood and the vessel wall play a crucial role in controlling vascular tone and homeostasis, particularly in determining the expression of pro- and anti-atherosclerotic genes. Many of these effects are mediated by changes in the generation and release of the vasodilator nitric oxide (NO) in response to hemodynamic stimuli exerted on the luminal surface of endothelial cells by the streaming blood (shear stress) and the cyclic strain of the vascular wall. The endothelial NO synthase (eNOS) is activated in response to fluid shear stress and numerous agonists via cellular events such as; increased intracellular Ca(2+), interaction with substrate and co-factors, as well as adaptor and regulatory proteins, protein phosphorylation, and through shuttling between distinct sub-cellular domains. Dysregulation of these processes leads to attenuated eNOS activity and reduced NO output which is a characteristic feature of numerous patho-physiological disorders such as diabetes and atherosclerosis. This review summarizes some of the recent findings relating to the molecular events regulating eNOS activity.
Fleming
Ingrid
I
Institute for Vascular Signalling, Centre for Molecular Medicine, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60596, Frankfurt am Main, Germany. fleming@em.uni-frankfurt.de
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000595:Amino Acid Sequence; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism; D034281:Dynamins / Q000502:physiology; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D000071756:Soluble Guanylyl Cyclase
D048868:Adaptor Proteins, Signal Transducing; D002147:Calmodulin; D051242:Caveolin 1; C098587:GAB1 protein, human; D018841:HSP90 Heat-Shock Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018160:Receptors, Cytoplasmic and Nuclear; D001708:Biopterins; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D011494:Protein Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D034281:Dynamins; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; C003402:sapropterin