Coptidis rhizoma extract protects against cytokine-induced death of pancreatic beta-cells through suppression of NF-kappa B activation.
- Author:
Eun Kyung KIM
1
;
Kang Beom KWON
;
Mi Jeong HAN
;
Mi Young SONG
;
Ji Hyun LEE
;
Na LV
;
Sun O KA
;
Seung Ryong YEOM
;
Young Dal KWON
;
Do Gon RYU
;
Kang San KIM
;
Jin Woo PARK
;
Raekil PARK
;
Byung Hyun PARK
Author Information
1. Department of Biochemistry, Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonju 561-756, Korea. bhpark@chonbuk.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
cell death;
Coptidis rhizoma extract;
cytokines;
drugs, Chinese herbal;
insulin secreting cells;
NF-kappa B;
nitric oxide
- MeSH:
Animals;
Cell Death/drug effects;
Cell Line;
Cell Nucleus/metabolism;
Cell Survival/drug effects;
Drugs, Chinese Herbal/*pharmacology;
Gene Expression Regulation, Enzymologic/drug effects;
Glucose/pharmacology;
I-kappa B Proteins/metabolism;
Insulin/secretion;
Insulin-Secreting Cells/*cytology/*drug effects/enzymology;
Interferon-gamma/*pharmacology;
Interleukin-1beta/*pharmacology;
Male;
NF-kappa B/*metabolism;
Nitric Oxide/biosynthesis;
Nitric Oxide Synthase Type II/genetics/metabolism;
Protein Transport/drug effects;
RNA, Messenger/genetics/metabolism;
Rats;
Rats, Sprague-Dawley
- From:Experimental & Molecular Medicine
2007;39(2):149-159
- CountryRepublic of Korea
- Language:English
-
Abstract:
We demonstrated previously that Coptidis rhizoma extract (CRE) prevented S-nitroso-N-acetylpenicillamine-induced apoptotic cell death via the inhibition of mitochondrial membrane potential disruption and cytochrome c release in RINm5F (RIN) rat insulinoma cells. In this study, the preventive effects of CRE against cytokine-induced beta-cell death was assessed. Cytokines generated by immune cells infiltrating pancreatic islets are crucial mediators of beta-cell destruction in insulin-dependent diabetes mellitus. The treatment of RIN cells with IL-1beta and IFN-gamma resulted in a reduction of cell viability. CRE completely protected IL-1beta and IFN-gamma-mediated cell death in a concentration-dependent manner. Incubation with CRE induced a significant suppression of IL-1beta and IFN-gamma-induced nitric oxide (NO) production, a finding which correlated well with reduced levels of the iNOS mRNA and protein. The molecular mechanism by which CRE inhibited iNOS gene expression appeared to involve the inhibition of NF-kappa B activation. The IL-1beta and IFN-gamma-stimulated RIN cells showed increases in NF-kappa B binding activity and p65 subunit levels in nucleus, and IkappaBalpha 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 responses to glucose in IL-1beta and IFN-gamma-treated islets.
