Curcumin dramatically enhances retinoic acid-induced superoxide generating activity via accumulation of p47-phox and p67-phox proteins in U937 cells
Curcumin dramatically enhances retinoic acid-induced superoxide generating activity via accumulation of p47-phox and p67-phox proteins in U937 cells
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DOI：
10.1016/j.bbrc.2010.03.136
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发表时间：
2010-04-23
影响因子：
3.1
通讯作者：
Nakayama, Tatsuo
中科院分区：
文献类型：
--
作者：
Kikuchi, Hidehiko;Kuribayashi, Futoshi;Nakayama, Tatsuo
细胞色素b558是吞噬细胞和B淋巴细胞超氧阴离子（O-2（-））生成系统的重要组成部分，由大的gp 91-phox和小的p22-phox亚基以及胞浆蛋白p40-、p47-和p67-phox组成。已知吞噬细胞中缺乏该系统会导致严重的危及生命的感染。在这里，我们描述了姜黄素，一种多酚负责黄色的咖喱香料姜黄，显着激活O-2（-）-生成系统在维甲酸（RA）诱导分化的人单核细胞白血病U937细胞的巨噬细胞样细胞。当U937细胞在RA和姜黄素存在下培养时，O-2（-）-产生活性比后者不存在时增加4倍以上。半定量RT-PCR结果显示，与单独RA处理相比，RA和姜黄素共同处理略微增强了五种组分的基因表达。另一方面，免疫印迹分析显示，与单独的RA治疗相比，RA和姜黄素的共同治疗引起p47-phox（至7倍）和p67-phox（至4倍）蛋白水平的显著积累。这些结果表明，姜黄素显着增强RA诱导的O-2（-）-产生活性，通过积累胞浆p47-phox和p67-phox蛋白在U937细胞。因此，它应该具有作为白血病治疗中的有效修饰剂和/或作为免疫增强剂的潜力。(C)2010年爱思唯尔公司All rights reserved.
The membrane bound cytochrome b558 composed of large gp91-phox and small p22-phox subunits, and cytosolic proteins p40-, p47- and p67-phox are important components of superoxide (O-2(-))-generating system in phagocytes and B lymphocytes. A lack of this system in phagocytes is known to cause serious life-threatening infections. Here, we describe that curcumin, a polyphenol responsible for the yellow color of curry spice turmeric, 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 curcumin, the O-2(-)-generating activity increased more than 4-fold compared with that in the absence of the latter. Semiquantitative RT-PCR showed that co-treatment with RA and curcumin slightly enhanced gene expressions of the five components compared with those of the RA-treatment only. On the other hand, immunoblot analysis revealed that co-treatment with RA and curcumin caused remarkable accumulation of protein levels of p47-phox (to 7-fold) and p67-phox (to 4-fold) compared with those of the RA-treatment alone. These results suggested that curcumin dramatically enhances RA-induced O-2(-)-generating activity via accumulation of cytosolic p47-phox and p67-phox proteins in U937 cells. Therefore, it should have the potential as an effective modifier in therapy of leukemia and/or as an immunopotentiator. (C) 2010 Elsevier Inc. All rights reserved.