Coptidis rhizoma extract protects against cytokine-induceddeath of pancreatic β-cells through suppression of NF-κBactivation

• Published in: Experimental & molecular medicine pp. 149 - 159
• Main Authors: 김은경/권강범, 한미정, 송미영, 이지현, 여나, 가선오, 염승룡, 권영달, 유도곤, 김강산, 박진우, 박래길, 박병현
• Format: Journal Article
• Language: Korean
• Published: 생화학분자생물학회 01.04.2007
• Subjects: 생화학
• ISSN: 1226-3613; 2092-6413

We demonstrated previously that Coptidis rhizoma extract (CRE) prevented S-nitroso-N-acetylpeni-cillamine-induced apoptotic cell death via the in-hibition of mitochondrial membrane potential dis-ruption and cytochrome c re lease in RINm5F (RIN) rat insulinoma cells. In this study, the preventive effects of CRE against cytokine-induced β-cell death was assessed. Cytokines generated by immune cells infiltrating pancreatic islets are crucial mediators of β-cell destruction in insulin-dependent diabetes mellitus. The treatment of RIN cells with IL-1β and IFN-γ resulted in a reduction of cell viability. CRE completely protected IL-1β and IFN-γ-mediated cell death in a concentration-dependent manner. Incu-bation with CRE induced a significant suppression of IL-1β and IFN-γ-induced nitric oxide (NO) production, a finding which correlated well with reduced levels of the iNOS mRNA and protein. The molecular mecha-nism by which CRE inhibited iNOS gene expression appeared to involve the inhibition of NF-κB activa-tion. The IL-1β and IFN-γ-stimulated RIN cells showed increases in NF-κB binding activity and p65 subunit levels in nucleus, and I κBα degradation in cytosol compared to unstimulated cells. Furthermore, the protective effects of CRE were verified via the observation of reduced NO generation and iNOS expression, and normal insulin-secretion res-ponses to glucose in IL-1 β and IFN-γ-treated islets. KCI Citation Count: 28