Inhibition of cytokine-mediated nitric oxide synthase expression in rat insulinoma cells by scoparone.
Cytokines produced by immune cells infiltrating pancreatic islets are important mediators of beta-cell destruction in insulin-dependent diabetes mellitus. Scoparone (6,7-dimethoxycoumarin) is known to have a wide range of pharmacological properties in vitro. In this study, the effects of scoparone on cytokine-induced beta-cell dysfunction were examined. Presence of scoparone significantly protected interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma)-mediated cytotoxicity of RINm5F, a rat insulinoma cell line, and preserved glucose-stimulated insulin secretion in rat pancreatic islets. Scoparone also resulted in a significant reduction in IL-1beta and IFN-gamma-induced nitric oxide (NO) production, a finding that correlated well with reduced levels of the inducible form of NO synthase (iNOS) mRNA and protein. The molecular mechanism by which scoparone inhibited iNOS gene expression appeared to involve the inhibition of NF-kappaB activation. These results revealed the possible therapeutic value of scoparone for the prevention of diabetes mellitus progression.
Kim
Eun Kyung
EK
Department of Biochemistry, Medical School, Chonbuk National University, Jeonju, Korea.
Kwon
Kang Beom
KB
Lee
Ju Hyung
JH
Park
Byung Hyun
BH
Park
Jin Woo
JW
Lee
Hern Koo
HK
Jhee
Eun Chung
EC
Yang
Jeong Yeh
JY
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D015536:Down-Regulation; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007340:Insulinoma; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology
D003374:Coumarins; D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D007328:Insulin; D053583:Interleukin-1beta; D016328:NF-kappa B; D009573:Nitrites; D014665:Vasodilator Agents; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; C018145:scoparone