Effect of thiol-containing molecule cysteamine on the induction of inducible nitric oxide synthase in hepatocytes.

Effect of thiol-containing molecule cysteamine on the induction of inducible nitric oxide synthase in hepatocytes. Research Abstract Details 

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Effect of thiol-containing molecule cysteamine on the induction of inducible nitric oxide synthase in hepatocytes. Abstract Text:

Takashi Ozaki,Masaki Kaibori,Kosuke Matsui,Katsuji Tokuhara,Hironori Tanaka,Yasuo Kamiyama,Mikio Nishizawa,Seiji Ito,Tadayoshi Okumura,Takashi Ozaki,Masaki Kaibori,Kosuke Matsui,Katsuji Tokuhara,Hironori Tanaka,Yasuo Kamiyama,Mikio Nishizawa,Seiji Ito,Tadayoshi Okumura,

BACKGROUND: Cysteamine, which is a known antioxidant and anti-inflammatory agent, is believed to be a key regulator of essential metabolic pathways in organisms. Cysteamine has beneficial effects in liver damaged by a variety of insults. During liver injury, inducible nitric oxide synthase (iNOS) is induced by lipopolysaccharide or proinflammatory cytokines, leading to excessive nitric oxide (NO) production. Accumulated evidence indicates that NO is an important factor associated with hepatic dysfunction. We examined whether cysteamine influences the induction of iNOS in hepatocytes. METHODS: Primary cultured rat hepatocytes were treated with interleukin (IL)-1beta in the presence and absence of cysteamine. NO production, iNOS induction, and iNOS signal were analyzed. RESULTS: IL-1beta stimulated the inhibitory protein kappaB (IkappaB)/nuclear factor kappaB (NFkappaB) pathway, resulting in the activation of NFkappaB (nuclear translocation and DNA binding), which was followed by the induction of iNOS and NO production. The addition of IL-1beta and cysteamine (1-4 mmol/L) markedly inhibited NO production, with a maximal effect at 4 mmol/L (80%-90% inhibition). Cysteamine also decreased the levels of iNOS protein and mRNA. Transfection experiments revealed that cysteamine decreased the transactivation activity of the iNOS promoter. An electrophoretic mobility shift assay demonstrated that cysteamine inhibited the activation of NFkappaB. Furthermore, cysteamine decreased the mRNA levels of the NFkappaB subunit p65 but increased those of the inhibitory protein IkappaB. CONCLUSIONS: These findings suggest that cysteamine inhibits iNOS induction at the step of NFkappaB activation. Further study is necessary to define the molecular basis of this effect of cysteamine on the regulation of NFkappaB and its pharmacologic implications.

Effect of thiol-containing molecule cysteamine on the induction of inducible nitric oxide synthase in hepatocytes. Publishing Authors By Initials

T Ozaki,M Kaibori,K Matsui,K Tokuhara,H Tanaka,Y Kamiyama,M Nishizawa,S Ito,T Okumura,T Ozaki,M Kaibori,K Matsui,K Tokuhara,H Tanaka,Y Kamiyama,M Nishizawa,S Ito,T Okumura,

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Effect of thiol-containing molecule cysteamine on the induction of inducible nitric oxide synthase in hepatocytes. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: JPEN. Journal of parenteral and enteral nutrition

VOLUME: 31

Page Numbers: 366-71; discussion 371-2

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ISSN: 0148-6071

DAY: 22

MONTH: 08

YEAR: 2007

Effect of thiol-containing molecule cysteamine on the induction of inducible nitric oxide synthase in hepatocytes. Information

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LANGUAGE: eng

NlmUniqueID: 7804134

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AFFILIATION: Department of Surgery, Kansai Medical University, Moriguchi, Osaka, Japan.

Country: United States

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MEDLINETA: JPEN J Parenter Enteral Nutr

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