Internalization of eNOS via caveolae regulates PAF-induced inflammatory hyperpermeability to macromolecules.

American Journal of Physiology. Heart and Circulatory Physiology
Fabiola A SánchezWalter N Durán

Abstract

Endothelial nitric oxide (NO) synthase (eNOS) is thought to regulate microvascular permeability via NO production. We tested the hypotheses that the expression of eNOS and eNOS endocytosis by caveolae are fundamental for appropriate signaling mechanisms in inflammatory endothelial permeability to macromolecules. We used bovine coronary postcapillary venular endothelial cells (CVECs) because these cells are derived from the microvascular segment responsible for the transport of macromolecules in inflammation. We stimulated CVECs with platelet-activating factor (PAF) at 100 nM and measured eNOS phosphorylation, NO production, and CVEC monolayer permeability to FITC-dextran 70 KDa (Dx-70). PAF translocated eNOS from plasma membrane to cytosol, induced changes in the phosphorylation state of the enzyme, and increased NO production from 4.3+/-3.8 to 467+/-22.6 nM. PAF elevated CVEC monolayer permeability to FITC-Dx-70 from 3.4+/-0.3 x 10(-6) to 8.5+/-0.4 x 10(-6) cm/s. The depletion of endogenous eNOS with small interfering RNA abolished PAF-induced hyperpermeability, demonstrating that the expression of eNOS is required for inflammatory hyperpermeability responses. The inhibition of the caveolar internalization by blocking caveolar...Continue Reading

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Citations

Apr 4, 2009·Proceedings of the National Academy of Sciences of the United States of America·Fabiola A SánchezWalter N Durán
Jul 16, 2011·The Journal of Biological Chemistry·Fabiola A SánchezWalter N Durán
May 14, 2010·Cardiovascular Research·Walter N DuránFabiola A Sánchez
Dec 14, 2011·Free Radical Biology & Medicine·Peter R Kvietys, D Neil Granger
Oct 1, 2013·IUBMB Life·Walter N DuránFabiola A Sánchez
Mar 10, 2010·Journal of Cellular Biochemistry·Roberta RamellaMaria Pia Gallo
Apr 20, 2018·British Journal of Pharmacology·Tatsuro Nakamura, Takahisa Murata
Jul 9, 2016·Circulation Research·Walter N Durán, Fabiola A Sánchez
Dec 10, 2013·Critical Care Medicine·Edwin A DeitchZoltan Spolarics
May 21, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Patricia ZamoranoFabiola A Sánchez
Feb 28, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Anita GuequénFabiola A Sánchez
Apr 17, 2019·Cell Communication and Signaling : CCS·Stephen R KochRyan J Stark
Mar 23, 2018·Molecular Biology of the Cell·Zhenlong ChenRichard D Minshall
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May 3, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Ji Yeon KimWonhee Suh
Oct 16, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Gaynor AguilarFabiola A Sánchez

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