NDLI: Differential regulation of inducible nitric oxide synthase by fibroblast growth factors and transforming growth factor beta in bovine retinal pigmented epithelial cells: inverse correlation with cellular proliferation.

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Differential regulation of inducible nitric oxide synthase by fibroblast growth factors and transforming growth factor beta in bovine retinal pigmented epithelial cells: inverse correlation with cellular proliferation.

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Differential regulation of inducible nitric oxide synthase by fibroblast growth factors and transforming growth factor beta in bovine retinal pigmented epithelial cells: inverse correlation with cellular proliferation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lepoivre, M. Becquet, F. Goureau, O. Courtois, Y.
Description	Author Affiliation: Goureau O ( Unité de Recherches Gérontologiques, Institut National de la Santé et de la Recherche Médicale U118, Paris, France.);
Abstract	Bovine retinal pigmented epithelial (RPE) cells express, after activation with interferon gamma (IFN-gamma) and lipopolysaccharide (LPS), an inducible nitric oxide synthase (NOS). Experiments were done to investigate the effects of the transforming growth factor beta 1, epidermal growth factor, and fibroblast growth factors (FGFs), which are abundant in the retina, on NOS activity. Transforming growth factor beta 1 slightly increases the production of nitrite, an oxidation product of NO, induced by LPS plus IFN-gamma, whereas acidic and basic FGFs markedly inhibit the nitrite release due to LPS/IFN-gamma in a concentration-dependent manner, and epidermal growth factor did not modify LPS/IFN-gamma-induced NOS activity. The growth factors alone did not stimulate nitrite release. We have attempted to elucidate the mechanism of FGF inhibition. Results with heparin, suramin, and tyrphostin suggest involvement of the high-affinity receptor for FGF in its inhibition of LPS/IFN-gamma-stimulated NOS activity. Continued stimulation of RPE cells with LPS/IFN-gamma was essential for the induction of NO synthesis, and maximal inhibition was obtained when FGF was present during stimulation with LPS/IFN-gamma, suggesting that FGF inhibits NOS induction. Furthermore, an antiproliferative action of NO was demonstrated by an inverse correlation between the amounts of nitrite or citrulline produced in response to different stimuli (LPS/IFN-gamma or LPS/IFN-gamma with growth factors) and the level of cellular proliferation. Similar inhibition of growth was obtained when RPE cells were incubated with an NO donor, sydnonimide. Because NO acts as a cytotoxic compound in the retina, FGF, by inhibiting the induction of NOS in RPE cells, may have beneficial effects in protecting the retina from cytokine and endotoxin-mediated tissue damage.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	9
Volume Number	90
Language	English
Publisher	National Academy of Sciences
Publisher Date	1993-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Amino Acid Oxidoreductases Metabolism Fibroblast Growth Factor 1 Pharmacology Fibroblast Growth Factor 2 Nitrites Pigment Epithelium Of Eye Enzymology Transforming Growth Factor Beta Tyrphostins Biosynthesis Animals Catechols Cells, Cultured Enzyme Induction Epidermal Growth Factor Heparin Interferon-gamma Kinetics Lipopolysaccharides Molsidomine Analogs & Derivatives Nitric Oxide Synthase Nitriles Drug Effects Recombinant Proteins Suramin Vasodilator Agents Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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