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(Circulation Research. 2006;99:793.)
© 2006 American Heart Association, Inc.

Editorials

A New Paradigm

Calcium Independent and Caveolae Internalization Dependent Release of Nitric Oxide by the Endothelial Nitric Oxide Synthase

Ghassan Bkaily, Pedro D’Orleans-Juste, Danielle Jacques

From the Department of Anatomy and Cell Biology (G.B., D.J.) and Pharmacology (P.D-.J.), Faculty of Medicine, University of Sherbrooke, Quebec, Canada.

Correspondence to G. Bkaily, Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Quebec, Canada, J1H 5N4. E-mail Ghassan.Bkaily@Usherbrooke.ca

See related article, pages 870–877

Key Words: caveolae • eNOS • NO • calcium • endothelial cells

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Caveolae, cholesterol rich microdomain platforms localized mostly at the cytoplasmic membrane of endothelial cells as well as other cell types, are importantly involved in cell signaling and enzymatic activity.^1–6 Caveolae also contain cationic amino acid transporter (CAT) which provide L-Arginine to the eNOS-Ca²⁺-Calmodulin complex toward the production of nitric oxide (NO).^1–6

Caveolin-1, a major caveolae-localized protein, represses markedly eNOS-dependent NO production by interfering with NADPH-dependent electron flux.³ Alteration in caveolin abundance or its subcellular location leads to the control of NO production.^5,6 Thus, it is clear, that the more the caveolin the less the NO, and inversely.³

The conventional paradigm supports the concept that eNOS–caveolin-1 interaction promotes inhibition of NO production, whereas increased intracellular Ca²⁺ activates Ca²⁺-Calmodulin which in turn disrupts the eNOS–caveolin-1 interaction and thus liberates the enzyme. This in turn promotes NO production.^1–6

A new paradigm is now suggested by Miniatis and colleagues⁷_, who elegantly demonstrated that NO production in pulmonary endothelial cells is significantly mediated by caveolae internalization and is independent of the increase of intracellular Ca²⁺.⁷ Furthermore, these authors clearly show that the albumin-binding protein gp60 is importantly involved in both caveolae internalization and consequently in the increase of the endothelial NOS dependent NO release.

In their study, Miniatis et al, adopted a strategy demonstrating, under specific experimental conditions, that the NO release following activation of eNOS activity by gp60 was Ca²⁺-independent.⁷ The fact that the intracellular loaded Ca²⁺ chelator BAPTA had no effect on NO production when compared with control supports . . . [Full Text of this Article]

Related Article:

Novel Mechanism of Endothelial Nitric Oxide Synthase Activation Mediated by Caveolae Internalization in Endothelial Cells

Nikolaos A. Maniatis, Viktor Brovkovych, Scott E. Allen, Theresa A. John, Ayesha N. Shajahan, Chinnaswamy Tiruppathi, Stephen M. Vogel, Randal A. Skidgel, Asrar B. Malik, and Richard D. Minshall
Circ. Res. 2006 99: 870-877. [Abstract] [Full Text] [PDF]

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