Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells.
10.4196/kjpp.2013.17.4.315
- Author:
Cha Kyung YOUN
1
;
Seon Joo PARK
;
Mei Hong LI
;
Min Young LEE
;
Kun Yeong LEE
;
Man Jin CHA
;
Ok Hyeun KIM
;
Ho Jin YOU
;
In Youp CHANG
;
Sang Pil YOON
;
Young Jin JEON
Author Information
1. DNA Damage Response Network Center, Chosun University, Kwangju 501-709, Korea. yjjeon@chosun.ac.kr
- Publication Type:Original Article
- Keywords:
beta cells;
ERK1/2;
iNOS;
NO
- MeSH:
Flavonoids;
Gene Expression;
Imidazoles;
Insulin-Secreting Cells;
Macrolides;
Negotiating;
Nitric Oxide Synthase Type II;
Pyridines;
Tumor Necrosis Factor-alpha
- From:The Korean Journal of Physiology and Pharmacology
2013;17(4):315-320
- CountryRepublic of Korea
- Language:English
-
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.
