Regulation of nerve growth factor release by nitric oxide through cyclic GMP pathway in cortical glial cells

Huabao Xiong, Kiyofumi Yamada, Hussam Jourdi, Meiko Kawamura, Nobuyuki Takei, Daiken Han, Toshitaka Nabeshima, Hiroyuki Nawa

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

In the present study, we found that s-nitroso-N-acetyl-DL-penicillamine, a spontaneous nitric oxide (NO) generator, dose-dependently inhibited basal nerve growth factor (NGF) release from mixed glial cells. To elucidate the function of endogenous NO in the regulation of NGF release, the mixed glial cells were stimulated with lipopolysaccharide (LPS) or LPS plus interferon- γ (IFNγ). The results showed that LPS alone induced NGF release and moderate NO production. However, costimulation with LPS plus IFNγ greatly enhanced NO production but significantly suppressed LPS-induced NGF release. When N(G)-monomethyl-L-arginine, an NOS inhibitor, was added to the culture, the suppression of NGF release by IFNγ was significantly reduced. Quantitative reverse transcription-polymerase chain reaction demonstrated S- nitroso-N-acetyl-DL-penicillamine was also able to inhibit the LPS-induced NGF mRNA expression. To understand-the different contributions of astroglia and microglia to this phenomenon, both cell types were purified. We found purified astroglia produced high amounts of NGF but low amounts of NO. However, purified microglia produced a large amount of NO but very low amounts of NGF after stimulation with LPS or LPS plus IFNγ. Our data also indicated the second messenger cyclic GMP, but not cyclic AMP, was able to inhibit basal NGF release. In vivo experiments confirmed that NGF protein level was significantly enhanced in rats treated with L-N(ω)-nitro-arginine methyl-ester and in endothelial NO synthase mutant mice. Taken together, we conclude NO derived mainly from microglia down-regulates NGF release from astroglia at the transcriptional level by stimulating cyclic GMP pathway.

Original languageEnglish
Pages (from-to)339-347
Number of pages9
JournalMolecular Pharmacology
Volume56
Issue number2
DOIs
Publication statusPublished - 01-01-1999
Externally publishedYes

Fingerprint

Cyclic GMP
Nerve Growth Factor
Neuroglia
Nitric Oxide
Lipopolysaccharides
Interferons
Microglia
Astrocytes
Penicillamine
Nitric Oxide Synthase Type III
Second Messenger Systems
Cyclic AMP
Reverse Transcription
Arginine
Down-Regulation
Polymerase Chain Reaction
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Xiong, Huabao ; Yamada, Kiyofumi ; Jourdi, Hussam ; Kawamura, Meiko ; Takei, Nobuyuki ; Han, Daiken ; Nabeshima, Toshitaka ; Nawa, Hiroyuki. / Regulation of nerve growth factor release by nitric oxide through cyclic GMP pathway in cortical glial cells. In: Molecular Pharmacology. 1999 ; Vol. 56, No. 2. pp. 339-347.
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Regulation of nerve growth factor release by nitric oxide through cyclic GMP pathway in cortical glial cells. / Xiong, Huabao; Yamada, Kiyofumi; Jourdi, Hussam; Kawamura, Meiko; Takei, Nobuyuki; Han, Daiken; Nabeshima, Toshitaka; Nawa, Hiroyuki.

In: Molecular Pharmacology, Vol. 56, No. 2, 01.01.1999, p. 339-347.

Research output: Contribution to journalArticle

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AU - Xiong, Huabao

AU - Yamada, Kiyofumi

AU - Jourdi, Hussam

AU - Kawamura, Meiko

AU - Takei, Nobuyuki

AU - Han, Daiken

AU - Nabeshima, Toshitaka

AU - Nawa, Hiroyuki

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