NAD(P)H:quinone oxidoreductase 1 (NQO1) localizes to the mitotic spindle in human cells.
NAD(P)H:quinone oxidoreductase 1 (NQO1) localizes to the mitotic spindle in human cells.
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DOI：
10.1371/journal.pone.0044861
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ross D
中科院分区：
文献类型：
--
作者：
Siegel D;Kepa JK;Ross D
NAD(P)H：苯二酮氧化还原酶1(NQO1)是一种含有苯二酚还原酶的FAD酶，可催化多种苯二酚的2电子还原反应。NQO1将对苯二酚还原为对苯二酚的2电子反应被认为是一个解毒过程，因为该反应绕过了高活性半对苯二酚的形成。NQO1在正常的上皮组织、内皮细胞、脂肪细胞以及许多人类实体肿瘤中高水平表达。除了作为一种苯醌还原酶的功能外，NQO1还被证明能还原超氧阴离子，调节S蛋白酶体对包括P53在内的蛋白质的降解。生化研究表明，NQO1主要位于胞浆中，但在细胞核中也发现了较低水平的NQO1。在这些研究中，我们使用免疫细胞化学和共聚焦成像技术证明了NQO1与细胞分裂过程中的有丝分裂纺锤体有关。在许多不同的人类细胞系中观察到NQO1与有丝分裂纺锤体的关系，包括未转化细胞(HUVEC)、永生化细胞系(HBMEC，16HBE)和癌症(胰腺癌，BXPC3)。双标记实验的共聚焦分析表明，NQO1与α-微管蛋白在有丝分裂纺锤体中共定位。在对BxPc-3人胰腺癌细胞的研究中，在NQO1抑制剂ES936或双香豆醇存在的情况下，NQO1与有丝分裂纺锤体的联系似乎没有变化，这表明NQO1可以与有丝分裂纺锤体结合，并仍然保持催化活性。对NQO1免疫染色的人肺鳞癌组织进行分析，发现NQO1在有丝分裂细胞的纺锤体中呈阳性染色。这项研究的目的是首次证明苯醌还原酶NQO1与人类细胞中有丝分裂纺锤体的关系。
NAD(P)H:quinone oxidoreductase 1 (NQO1) is an FAD containing quinone reductase that catalyzes the 2-electron reduction of a broad range of quinones. The 2-electron reduction of quinones to hydroquinones by NQO1 is believed to be a detoxification process since this reaction bypasses the formation of the highly reactive semiquinone. NQO1 is expressed at high levels in normal epithelium, endothelium and adipocytes as well as in many human solid tumors. In addition to its function as a quinone reductase NQO1 has been shown to reduce superoxide and regulate the 20 S proteasomal degradation of proteins including p53. Biochemical studies have indicated that NQO1 is primarily located in the cytosol, however, lower levels of NQO1 have also been found in the nucleus. In these studies we demonstrate using immunocytochemistry and confocal imaging that NQO1 was found associated with mitotic spindles in cells undergoing division. The association of NQO1 with the mitotic spindles was observed in many different human cell lines including nontransformed cells (astrocytes, HUVEC) immortalized cell lines (HBMEC, 16HBE) and cancer (pancreatic adenocarcinoma, BXPC3). Confocal analysis of double-labeling experiments demonstrated co-localization of NQO1with alpha-tubulin in mitotic spindles. In studies with BxPc-3 human pancreatic cancer cells the association of NQO1 with mitotic spindles appeared to be unchanged in the presence of NQO1 inhibitors ES936 or dicoumarol suggesting that NQO1 can associate with the mitotic spindle and still retain catalytic activity. Analysis of archival human squamous lung carcinoma tissue immunostained for NQO1 demonstrated positive staining for NQO1 in the spindles of mitotic cells. The purpose of this study is to demonstrate for the first time the association of the quinone reductase NQO1 with the mitotic spindle in human cells.
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影响因子：
11.2
作者：
Cao, Jia-ning;Shafee, Norazizah;Stanbridge, Eric J.
通讯作者：
Stanbridge, Eric J.
影响因子：
5.1
作者：
Pfeiffer, E;Metzler, M
通讯作者：
Metzler, M
影响因子：
8
作者：
Patrick, B. A.;Gong, X.;Jaiswal, A. K.
通讯作者：
Jaiswal, A. K.
影响因子：
5.8
作者：
Siegel D;Yan C;Ross D
通讯作者：
Ross D
DOI：
10.1016/j.bbrc.2011.07.101
发表时间：
2011-08-26
影响因子：
3.1
作者：
Bui, Chi-Bao;Shin, Jaekyoon
通讯作者：
Shin, Jaekyoon