The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells

  • Youn, Cha Kyung (DNA Damage Response Network Center, Chosun University) ;
  • Park, Seon Joo (DNA Damage Response Network Center, Chosun University) ;
  • Li, Mei Hong (Department of Pharmacology, School of Medicine, Chosun University) ;
  • Lee, Min Young (DNA Damage Response Network Center, Chosun University) ;
  • Lee, Kun Yeong (Department of Pharmacology, School of Medicine, Chosun University) ;
  • Cha, Man Jin (Department of Pharmacology, School of Medicine, Chosun University) ;
  • Kim, Ok Hyeun (Department of Pharmacology, School of Medicine, Chosun University) ;
  • You, Ho Jin (DNA Damage Response Network Center, Chosun University) ;
  • Chang, In Youp (DNA Damage Response Network Center, Chosun University) ;
  • Yoon, Sang Pil (Department of Anatomy, School of Medicine, Jeju National University) ;
  • Jeon, Young Jin (DNA Damage Response Network Center, Chosun University)
  • Received : 2013.03.25
  • Accepted : 2013.07.05
  • Published : 2013.08.30
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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-$1{\beta}$). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-${\kappa}B$/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.

Keywords

References

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