Sesamin increases heme oxygenase-1 protein in RAW 264.7 macrophages through inhibiting its ubiquitination process

被引：15

作者：

Fukunaga, Mizuki ^{[1
]}

Ohnishi, Masatoshi ^{[1
,2
]}

Shiratsuchi, Ayano ^{[1
]}

Kawakami, Takuya ^{[1
]}

Takahashi, Madoka ^{[1
]}

Motomura, Misato ^{[1
]}

Egusa, Kyohei ^{[1
]}

Urasaki, Tomoka ^{[2
]}

Inoue, Atsuko ^{[1
,2
]}

机构：

[1] Fukuyama Univ, Fac Pharm & Pharmaceut Sci, Dept Pharmacotherapeut, Fukuyama, Hiroshima 7290292, Japan

[2] Fukuyama Univ, Grad Sch Pharm & Pharmaceut Sci, Dept Pharmacotherapeut, Fukuyama, Hiroshima 7290292, Japan

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2014年 / 741卷

关键词：

Sesamin; Heme oxygenase-1; Ubiquitination; Macrophage; NITRIC-OXIDE SYNTHASE; FACTOR-KAPPA-B; MURINE MACROPHAGES; EXPRESSION; ACTIVATION; PATHWAY; NEUROPROTECTION; STRESS; DEGRADATION; MICROGLIA;

D O I：

10.1016/j.ejphar.2014.08.015

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Sesamin is a major component in lignans of sesame seed oil, known to possess potent anti-oxidative capacity. In this study, the variation of heme oxygenase (HO)-1, a kind of anti-oxidative enzyme, by sesamin in murine macrophage cell line RAW 264.7 cells was investigated. Lipopolysaccharide (LPS: 10 mu g/ml) exposure tended to increase HO-1 protein expression. Co-treatment with 100 mu M sesamin for 12 h up-regulated the HO-1 protein level increased by LPS, however, HO-1 mRNA was unaffected. Sesamin delayed the reversal, by the protein synthesis inhibitor cycloheximide (1 mu M), of the LPS-induced increase of HO-1 protein level. Meanwhile, sesamin suppressed LPS-induced expression of inducible nitric oxide (NO) synthase (iNOS) protein and associated NO release. LPS-induced increase of iNOS protein expression was also reversed by cycloheximide, which was not affected by sesamin, unlike HO-1. To clarify the mechanisms that underlie the up-regulation of HO-1 protein level by sesamin, the human embryonic kidney (HEK) 293 T cell line transfected with Flag-ragged HO-1 was used A proteasome inhibitor, MG-132 (10 mu M), stabilized HO-1 protein in HEK 293T cells. Co-treatment with sesamin decreased ubiquitinated HO-1 protein accumulation by MG-132. However, sesamin did not affect the proteasome activity. These findings suggest that sesamin disturbs the degradation of HO-1 protein through inhibiting its ubiquitination, resulting in HO-1 protein up-regulation. (C) 2014 Elsevier B.V. All rights reserved

引用

页码：214 / 221

页数：8

共 28 条

[1] Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages [J].