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KMID : 0811720130170040315
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Korean Journal of Physiology & Pharmacology
2013 Volume.17 No. 4 p.315 ~ p.320
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Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells
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Youn Cha-Kyung
Park Seon-Joo
Li Mei-Hong
Lee Min-Young
Lee Kun-Yeong
Cha Man-Jin
Kim Ok-Hyeun
You Ho-Jin
Chang In-Youp
Yoon Sang-Pil
Jeon Young-Jin
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Abstract
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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-?, IFN-?, and IL-1?). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-?B/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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KEYWORD
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? cells, ERK1/2, iNOS, NO
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