Induction of Glial Fibrillary Acidic Protein Expression in Astrocytes by Nitric Oxide

Increased expression of glial fibrillary acidic protein (GFAP) represents astroglial activation and gliosis during neurodegeneration. However, the molecular mechanism behind increased expression of GFAP in astrocytes is poorly understood. The present study was undertaken to explore the role of nitri...

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Main Authors: Brahmachari, Saurav, Fung, Yiu K., Pahan, Kalipada
Formato: Artigo
Idioma:English
Publicado em: Society for Neuroscience 2006
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Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC1963412/
https://ncbi.nlm.nih.gov/pubmed/16672668
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1523/JNEUROSCI.5480-05.2006
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spelling pubmed-19634122007-09-01 Induction of Glial Fibrillary Acidic Protein Expression in Astrocytes by Nitric Oxide Brahmachari, Saurav Fung, Yiu K. Pahan, Kalipada J Neurosci Articles Increased expression of glial fibrillary acidic protein (GFAP) represents astroglial activation and gliosis during neurodegeneration. However, the molecular mechanism behind increased expression of GFAP in astrocytes is poorly understood. The present study was undertaken to explore the role of nitric oxide (NO) in the expression of GFAP. Bacterial lipopolysachharides (LPSs) induced the production of NO and the expression of GFAP in mouse primary astrocytes. Either a scavenger of NO [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO)] or an inhibitor of inducible nitric oxide synthase [l-N6-(I-iminoethyl)-lysine hydrochloride] blocked this induction of GFAP expression. Similarly, other inducers of NO production such as interferon-γ, interleukin-1β, human immunodeficiency virus type 1 gp120, fibrillar amyloid β peptides, and double-stranded RNA (polyinosinic-polycytidilic acid) also induced the expression of GFAP through NO. The role of NO in the expression of GFAP was supported further by increased expression of GFAP by S-nitroso glutathione (GSNO), an NO donor. Interestingly, inhibition of nuclear factor κB (NF-κB) suppressed LPS- but not GSNO-induced expression of GFAP, suggesting that NO does not require NF-κB to induce GFAP and that NF-κB functions upstream of NO production. However, inhibition of LPS- and GSNO-induced expression of GFAP either by NS-2028 [a specific inhibitor of guanylate cyclase (GC)] or by KT5823 [a specific inhibitor of cGMP-activated protein kinase (PKG)], and induction of GFAP expression by either 8-Br cGMP (a cell-permeable cGMP analog) or MY-5445 (a specific inhibitor of cGMP phosphodiesterase) suggests that NO induces GFAP via GC-cGMP-PKG. This study illustrates a novel biological role of NO in regulating the expression of GFAP in astrocytes through the GC-cGMP-PKG pathway that may participate in the pathogenesis of neurodegenerative disorders. Society for Neuroscience 2006-05-03 /pmc/articles/PMC1963412/ /pubmed/16672668 http://dx.doi.org/10.1523/JNEUROSCI.5480-05.2006 Text en Copyright © 2006 Society for Neuroscience 0270-6474/06/264930-10$15.00/0
institution US National Library of Medicine
collection PubMed Central
language English
format Article
topic Articles
spellingShingle Articles
Brahmachari, Saurav
Fung, Yiu K.
Pahan, Kalipada
Induction of Glial Fibrillary Acidic Protein Expression in Astrocytes by Nitric Oxide
description Increased expression of glial fibrillary acidic protein (GFAP) represents astroglial activation and gliosis during neurodegeneration. However, the molecular mechanism behind increased expression of GFAP in astrocytes is poorly understood. The present study was undertaken to explore the role of nitric oxide (NO) in the expression of GFAP. Bacterial lipopolysachharides (LPSs) induced the production of NO and the expression of GFAP in mouse primary astrocytes. Either a scavenger of NO [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO)] or an inhibitor of inducible nitric oxide synthase [l-N6-(I-iminoethyl)-lysine hydrochloride] blocked this induction of GFAP expression. Similarly, other inducers of NO production such as interferon-γ, interleukin-1β, human immunodeficiency virus type 1 gp120, fibrillar amyloid β peptides, and double-stranded RNA (polyinosinic-polycytidilic acid) also induced the expression of GFAP through NO. The role of NO in the expression of GFAP was supported further by increased expression of GFAP by S-nitroso glutathione (GSNO), an NO donor. Interestingly, inhibition of nuclear factor κB (NF-κB) suppressed LPS- but not GSNO-induced expression of GFAP, suggesting that NO does not require NF-κB to induce GFAP and that NF-κB functions upstream of NO production. However, inhibition of LPS- and GSNO-induced expression of GFAP either by NS-2028 [a specific inhibitor of guanylate cyclase (GC)] or by KT5823 [a specific inhibitor of cGMP-activated protein kinase (PKG)], and induction of GFAP expression by either 8-Br cGMP (a cell-permeable cGMP analog) or MY-5445 (a specific inhibitor of cGMP phosphodiesterase) suggests that NO induces GFAP via GC-cGMP-PKG. This study illustrates a novel biological role of NO in regulating the expression of GFAP in astrocytes through the GC-cGMP-PKG pathway that may participate in the pathogenesis of neurodegenerative disorders.
author Brahmachari, Saurav
Fung, Yiu K.
Pahan, Kalipada
author_facet Brahmachari, Saurav
Fung, Yiu K.
Pahan, Kalipada
author_sort Brahmachari, Saurav
title Induction of Glial Fibrillary Acidic Protein Expression in Astrocytes by Nitric Oxide
title_short Induction of Glial Fibrillary Acidic Protein Expression in Astrocytes by Nitric Oxide
title_full Induction of Glial Fibrillary Acidic Protein Expression in Astrocytes by Nitric Oxide
title_fullStr Induction of Glial Fibrillary Acidic Protein Expression in Astrocytes by Nitric Oxide
title_full_unstemmed Induction of Glial Fibrillary Acidic Protein Expression in Astrocytes by Nitric Oxide
title_sort induction of glial fibrillary acidic protein expression in astrocytes by nitric oxide
publisher Society for Neuroscience
publisher_facet Society for Neuroscience
publishDate 2006
url https://ncbi.nlm.nih.gov/pmc/articles/PMC1963412/
https://ncbi.nlm.nih.gov/pubmed/16672668
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1523/JNEUROSCI.5480-05.2006
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