HSCARG inhibits NADPH oxidase activity through regulation of the expression of p47phox.

HSCARG inhibits NADPH oxidase activity through regulation of the expression of p47phox.
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HSCARG通过调节p47phox的表达来抑制NADPH氧化酶活性。

DOI:
10.1371/journal.pone.0059301
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Zheng X
Zheng X
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xiao W;Peng Y;Liu Y;Li Z;Li S;Zheng X

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烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶催化电子从NADPH转移到O2,O2是非吞噬细胞中活性氧(ROS)的主要来源。过量的ROS是有毒的;因此,保持细胞内ROS的稳态可以保护细胞免受氧化损伤。因此,进一步了解活性氧稳态调节的分子机制具有重要意义。人HSCARG蛋白是一种新发现的氧化感受器,是NF-κB的负调节因子。我们发现HSCARG通过抑制NADPH氧化酶亚基p47 phox的mRNA和蛋白表达来抑制细胞ROS的产生。相反,shRNA介导的HSCARG敲低增加内源性p47 phox表达水平。HSCARG对p47 phox缺失细胞ROS产生无明显影响。此外,HSCARG通过抑制NF-κB活性来调节p47 phox。我们的研究结果确定HSCARG作为一种新的调节NADPH氧化酶的活性和活性氧稳态的调节。
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase catalyzes the transfer of electrons from NADPH to O2, which is the main source of reactive oxygen species (ROS) in nonphagocytic cells. Excess ROS are toxic; therefore, keeping ROS in homeostasis in cells can protect cells from oxidative damage. It is meaningful to further understand the molecular mechanism by which ROS homeostasis is mediated. Human protein HSCARG is a newly identified oxidative sensor and a negative regulator of NF-κB. Here, we find that HSCARG represses the cellular ROS generation through inhibiting mRNA and protein expression of p47phox, a subunit of NADPH oxidase. In contrast, shRNA-mediated HSCARG knockdown increases endogenous p47phox expression level. And HSCARG has no obvious effect on ROS production in p47phox-depleted cells. Furthermore, HSCARG regulates p47phox through inhibition of NF-κB activity. Our findings identify HSCARG as a novel regulator in regulation of the activity of NADPH oxidase and ROS homeostasis.
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