Suppression of iNOS expression by fucoidan is mediated by regulation of p38 MAPK, JAK/STAT, AP-1 and IRF-1, and depends on up-regulation of scavenger receptor B1 expression in TNF-α- and IFN-γ-stimulated C6 glioma cells

被引：69

作者：

Do, Hang ^{[1
]}

Pyo, Suhkneung ^{[1
]}

Sohn, Eun-Hwa ^{[2
]}

机构：

[1] Sungkyunkwan Univ, Coll Pharm, Div Immunopharmacol, Suwon 440746, Kyunggi Do, South Korea

[2] Kangwon Natl Univ, Dept Herbal Med Resource, Inst Biosci & Biotechnol, Gangwon Do 245711, South Korea

来源：

JOURNAL OF NUTRITIONAL BIOCHEMISTRY | 2010年 / 21卷 / 08期

关键词：

Fucoidan; iNOS; p38; SRB1; Glia; NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; ACTIVATED PROTEIN-KINASE; DENSITY-LIPOPROTEIN BINDING; BETA-AMYLOID FIBRILS; SIGNALING PATHWAYS; KAPPA-B; ALZHEIMERS-DISEASE; INTERFERON-GAMMA; NERVOUS-SYSTEM;

D O I：

10.1016/j.jnutbio.2009.03.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

In neurodegenerative disorders, activated glial cells overproduce nitric oxide (NO), which causes neurotoxicity. Inducible NO synthase (iNOS) is a potential therapeutic target in neurodegenerative diseases. Here, we examined the action of fucoidan, a high-molecular-weight sulfated polysaccharide, on tumor necrosis factor-alpha (TNF-alpha)- and interferon-gamma (IFN-gamma)-induced NO production in C6 glioma cells. Fucoidan suppressed TNF-alpha- and IFN-gamma-induced NO production and iNOS expression. In addition, fucoidan inhibited TNF-alpha- and IFN-gamma-induced AP-1, IRF-1, JAK/STAT and p38 mitogen-activated protein kinase (MAPK) activation and induced scavenger receptor B1 (SR-B1) expression. Blocking of SR-B1 did not reverse the inhibitory effect of fucoidan on TNF-alpha- and IFN-gamma- stimulated NO production. However, inhibition of SR-B1 expression by siRNA increased iNOS expression and p38 phosphorylation in TNF-alpha- and IFN-gamma-stimulated C6 cells. Overall. p38 MAPK, AP-1, JAK/STAT and IRF-1 play an important role in the inhibitory effect of fucoidan on TNF-alpha- and IFN-gamma-stimulated NO production, and intracellular SR-B1 expression may be related to the inhibition of iNOS expression by fucoidan via regulation of p38 phosphorylation. The present results also suggest that fucoidan could be a potential therapeutic agent for treating inflammatory-related neuronal injury in neurological disorders. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：671 / 679

页数：9

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