Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells.
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-α, IFN-γ, and IL-1β). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-κB/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.
DNA Damage Response Network Center, Chosun University, Kwangju 501-709, Korea. ; Department of Pharmacology, School of Medicine, Chosun University, Gwangju 501-759, Korea.
Cha Kyung
CK
Youn
Seon Joo
SJ
Park
Mei Hong
MH
Li
Min Young
MY
Lee
Kun Yeong
KY
Lee
Man Jin
MJ
Cha
Ok Hyeun
OH
Kim
Ho Jin
HJ
You
In Youp
IY
Chang
Sang Pil
SP
Yoon
Young Jin
YJ
Jeon
ERK1/2; NO; iNOS; β cells