Resveratrol strongly enhances the retinoic acid-induced superoxide generating activity via up-regulation of gp91-phox gene expression in U937 cells
Resveratrol strongly enhances the retinoic acid-induced superoxide generating activity via up-regulation of gp91-phox gene expression in U937 cells
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DOI：
10.1016/j.bbrc.2017.11.161
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发表时间：
2018-01-01
影响因子：
3.1
通讯作者：
Kuribayashi, Futoshi
中科院分区：
文献类型：
--
作者：
Kikuchi, Hidehiko;Mimuro, Hitomi;Kuribayashi, Futoshi
膜结合型细胞色素b(558)是吞噬细胞超氧化物(O-2(-))生成系统的重要组成部分，由gp91-Phox和p22-Phox蛋白以及胞浆蛋白p40-、p47-和p67-Phox组成。在此，我们描述了白藜芦醇，一种属于二苯乙烯类化合物的多效性植物化学物质，在维甲酸(RA)诱导人单核细胞白血病U937细胞向巨噬细胞样细胞分化的过程中，显著激活了O-2(-)生成系统。当U937细胞在维甲酸和白藜芦醇存在的情况下培养时，O-2(-)的产生活性比在没有白藜芦醇的情况下增加5倍以上。半定量RT-PCR结果显示，与单独使用RA相比，RA和白藜芦醇联合处理可显著提高gp91-Phox的转录水平。另一方面，免疫印迹分析显示，与RA单独处理相比，RA和白藜芦醇联合处理导致gp91-Phox(4倍)、p22-Phox(5倍)和P47-Phox(4倍)蛋白水平显著增加。此外，芯片实验表明，白藜芦醇通过促进组蛋白H3基因启动子区域染色质内Lys 9残基和Lys-14残基的乙酰化来增强gp91-Phox基因的表达。这些结果表明，白藜芦醇通过上调gp91-Phox基因在U937细胞中的表达，增强了RA诱导的O-2(-)生成活性。(C)2017 Elsevier Inc.保留所有权利。
The membrane bound cytochrome b(558) composed of gp91-phox and p22-phox proteins, and cytosolic proteins p40-, p47-and p67-phox are important components of superoxide (O-2(-))-generating system in phagocytes. Here, we describe that resveratrol, a pleiotropic phytochemical belonging to the stilbenoids, dramatically activates the O-2(-)-generating system during retinoic acid (RA)-induced differentiation of human monoblastic leukemia U937 cells to macrophage-like cells. When U937 cells were cultured in the presence of RA and resveratrol, the O-2(-)-generating activity increased more than 5-fold compared with that in the absence of the latter. Semiquantitative RT-PCR showed that co-treatment with RA and resveratrol strongly enhanced transcription of the gp91-phox compared with those of the RA-treatment only. On the other hand, immunoblot analysis revealed that co-treatment with RA and resveratrol caused remarkable accumulation of protein levels of gp91-phox (to 4-fold), p22-phox (to 5-fold) and p47-phox (to 4-fold) compared with those of the RA-treatment alone. In addition, ChIP assay suggested that resveratrol participates in enhancing the gene expression of gp91-phox via promoting acetylation of Lys 9 residues and Lys-14 residues of histone H3 within chromatin around the promoter regions of the gene. These results suggested that resveratrol strongly enhances the RA-induced O-2(-)-generating activity via up regulation of gp91-phox gene expression in U937 cells. (C) 2017 Elsevier Inc. All rights reserved.