Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells
The Korean Journal of Physiology and Pharmacology
;
: 315-320, 2013.
Artigo
em Inglês
| WPRIM
| ID: wpr-727714
ABSTRACT
Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM TNF-alpha, IFN-gamma, and IL-1beta). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-kappaB/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.
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Índice:
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Assunto principal:
Piridinas
/
Flavonoides
/
Expressão Gênica
/
Fator de Necrose Tumoral alfa
/
Negociação
/
Macrolídeos
/
Células Secretoras de Insulina
/
Óxido Nítrico Sintase Tipo II
/
Imidazóis
Idioma:
Inglês
Revista:
The Korean Journal of Physiology and Pharmacology
Ano de publicação:
2013
Tipo de documento:
Artigo
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