Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
권호 표지

Coptidis rhizoma extract protects against cytokine-induced death of pancreatic $\beta$-cells through suppression of NF-$\kappa$B activation

Kim, Eun-Kyung;Kwon, Kang-Beom;Han, Mi-Jeong;Song, Mi-Young;Lee, Ji-Hyun;Lv, Na;Ka, Sun-O;Yeom, Seung-Ryong;Kwon, Young-Dal;Ryu, Do-Gon;Kim, Kang-San;Park, Jin-Woo;Park, Rae-Kil;Park, Byung-Hyun

  • Published : 20070400
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Abstract

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.

Keywords

References

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