Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2007 Jul 15;75(2):247-60.
doi: 10.1016/j.cardiores.2007.03.023. Epub 2007 Apr 3.

Life history of eNOS: partners and pathways

David M Dudzinski  1 , Thomas Michel
Affiliations
Review

Life history of eNOS: partners and pathways

David M Dudzinski et al. Cardiovasc Res. .

Abstract

The complex regulation of eNOS (endothelial nitric oxide synthase) in cardiovascular physiology occurs at multiple stages. eNOS mRNA levels are controlled both at the transcriptional and post-transcriptional phases, and epigenetic mechanisms appear to modulate tissue-specific eNOS expression. The eNOS enzyme reversibly associates with a diverse family of protein partners that regulate eNOS sub-cellular localization, catalytic function, and biological activity. eNOS enzyme activity and sub-cellular localization are intimately controlled by post-translational modifications including phosphorylation, nitrosylation, and acylation. The multiple extra-cellular stimuli affecting eNOS function coordinate their efforts through these key modifications to dynamically control eNOS and NO bioactivity in the vessel wall. This review will focus on the biochemical partners and perturbations of the eNOS protein as this vital enzyme undergoes modulation by diverse signal transduction pathways in the vascular endothelium.

PubMed Disclaimer

Figures

None
Dynamic relationship between key eNOS post-translational modifications
This figure demonstrates some of the interelationships of caveolin binding, calmodulin binding, acylation, and phosphorylation on eNOS activity. Panel 1 shows quiescent eNOS anchored to caveolae by myristoylation and palmitoylation (blue and red chains respectively); in this state eNOS is inhibited by caveolin binding, inhibitory phosphorylation at serine 116, and nitrosylation at cysteines 96 and 101. Panel 2 shows displacement of caveolin binding by calcium-calmodulin. Denitrosylation plus stimulatory phosphorylation at serine 1179 enhances enzyme activity in panel 3, accompanied by hsp90 binding. After prolonged agonist stimulation, eNOS becomes depalmitoylated and translocates from peripheral to internal membranes. eNOS is inactivated by calmodulin dissociation allowing re-binding of caveolin, accompanied by re-nitrosylation of the enzyme and dephosphorylation of eNOS at its stimulatory phosphorylation sites. See text for details.
See this image and copyright information in PMC

References

    1. Dudzinski DM, Michel T. The Vascular Biology of Nitric Oxide and Nitric Oxide Synthases. In: Colman RW, George JN, Goldhaber SZ, Marder VJ, Clowes AW, editors. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 5. Philadelphia: Lippincott Williams & Wilkins; 2005. pp. 653–66.
    1. Dudzinski DM, Igarashi J, Greif DM, Michel T. The regulation and pharmacology of endothelial nitric oxide synthase. Annu Rev Pharmacol Toxicol. 2006;46:235–76. - PubMed
    1. Lowenstein CJ, Michel T. What’s in a name? eNOS and anaphylactic shock. J Clin Invest. 2006;116:2075–8. - PMC - PubMed
    1. Kleinbongard P, Schulz R, Rassaf T, Lauer T, Dejam A, Jax T, et al. Red blood cells express a functional endothelial nitric oxide synthase. Blood. 2006;107:2943–51. - PubMed
    1. de Frutos T, Sánchez de Miguel L, Farré J, Gómez J, Romero J, Marcos-Alberca P, et al. Expression of an endothelial-type nitric oxide synthase isoform in human neutrophils: modification by tumor necrosis factor-alpha and during myocardial infarction. J Am Coll Cardiol. 2001;37:800–7. - PubMed

Substances