Forskolin inhibits expression of inducible nitric oxide synthase mRNA via inhibiting the mitogen activated protein kinase in C6 cells

Brain Research. Molecular Brain Research
J S WonH W Suh

Abstract

This study has demonstrated the mechanism of protein kinase A (PKA)-dependent inhibition of astrocytic nitric oxide production and inducible NO synthase mRNA expression induced by lipopolysaccharide. In C6 glioma cells, the stimulation with lipopolysaccharide (LPS; 1 microg/ml) evoked increases of nitric oxide (NO) production, NO synthase (iNOS) mRNA expression, phosphorylation of p38 mitogen activated protein kinase (p-p38), and the activation of NF kappa B. LPS-induced NO production and iNOS mRNA expression were inhibited by the pretreatment with forskolin (FSK; 5 microM) in a dose-dependent manner, and which were reversed by PKA inhibition by compound H89. Furthermore, LPS-induced increases of p-p38, but not activation of NF kappa B, were also reduced by FSK and H89 reversed the FSK-induced inhibition response. The dose-dependent inhibition of NO production and iNOS mRNA expression by compound SB203580 (p38 inhibitor) suggests the participation of p38 in PKA-dependent inhibition of LPS-induced NO production and iNOS mRNA expression. However, the activation of NF kappa B by LPS also not affected by SB203580. Therefore, our results suggest that, in C6 glioma cells, LPS-induced NO production and iNOS gene expression may be regu...Continue Reading

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Citations

Nov 5, 2002·Brain Research. Molecular Brain Research·Sun Young ParkKyoungho Suk
Dec 4, 2003·Neurochemistry International·Serafina SalvatiMassimo Sanchez
Oct 25, 2002·Toxicology in Vitro : an International Journal Published in Association with BIBRA·M M Garber, A S Heiman
Jan 23, 2008·Expert Opinion on Therapeutic Targets·Charles J Malemud, Andrew H Miller
Dec 14, 2004·International Immunopharmacology·Xiu Li BiChun Fu Wu
Sep 19, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Andrew H Miller, Charles L Raison
Aug 15, 2018·The Journal of Pharmacology and Experimental Therapeutics·Abubakr MossaLysanne Campeau
Mar 8, 2002·American Journal of Physiology. Endocrinology and Metabolism·Zhongmin MaSasanka Ramanadham

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