Poly (ADP-Ribose) Polymerase 1 Mediated Arginase II Activation Is Responsible for Oxidized LDL-Induced Endothelial Dysfunction.
Poly (ADP-Ribose) Polymerase 1 Mediated Arginase II Activation Is Responsible for Oxidized LDL-Induced Endothelial Dysfunction.
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聚（ADP-核糖）聚合酶 1 介导的精氨酸酶 II 激活是氧化 LDL 诱导的内皮功能障碍的原因
DOI：
10.3389/fphar.2018.00882
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发表时间：
2018
影响因子：
5.6
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Wang Q;Zhao T;Zhang W;Yu W;Liu B;Wang Z;Qiao W;Lu Q;Wang A;Zhang M
It is well known that arginase II leads to decreased synthesis of nitric oxide (NO) by competing with endothelial nitric oxide synthase (eNOS) for their same substrate L-arginine. However, the regulatory mechanisms of arginase II production remain unclear. In this study, we hypothesized that poly- (ADP-ribose) transferase/polymerase-1 (PARP-1) may be a critical factor responsible for ox-LDL (oxidized Low Density Lipoprotein)-enhanced arginase II activity. We used serial deletions within plasmid constructs and found that a core promoter region of arginase II was located at the element of -774 to -738 bp and PARP-1 was identified specifically binding to this region. Inhibition of PARP-1 markedly reduced the endogenous arginase II expression and enhanced eNOS and NO production. Similarly, ox-LDL-induced increase in arginase II production and eNOS and NO reduction was substantially abolished by PARP-1 inhibition both in vitro and in vivo. Significant decrease in arginase II expression and increase in eNOS expression and NO levels, as well as improved endothelial function were observed in PARP-1-/- mice. The underlying mechanisms of ox-LDL-induced changes of PARP-1 expression involved migration of phosphorylated ERK2 into nuclei and direct interaction with PARP-1 which dramatically enhanced PARP-1 production, followed by histone acetylation to activate arginase II transcription process. Our studies demonstrated for the first time that PARP-1 regulates basal transcription process and ox-LDL-induced up-regulation of arginase II. These results demonstrated that PARP-1 offers a promising therapeutic target for endothelial dysfunction and atherosclerosis.
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影响因子：
37.8
作者：
Sun C;Wu MH;Yuan SY
通讯作者：
Yuan SY
影响因子：
3.7
作者：
Hans CP;Feng Y;Naura AS;Zerfaoui M;Rezk BM;Xia H;Kaye AD;Matrougui K;Lazartigues E;Boulares AH
通讯作者：
Boulares AH
DOI：
10.1083/jcb.200512083
发表时间：
2006-03-27
期刊：
The Journal of cell biology
影响因子：
--
作者：
Percipalle P;Visa N
通讯作者：
Visa N
影响因子：
3.3
作者：
Winters, B;Mo, ZP;Berkowitz, DE
通讯作者：
Berkowitz, DE
影响因子：
37.8
作者：
Oumouna-Benachour, Karine;Hans, Chetan P.;Boulares, A. Hamid
通讯作者：
Boulares, A. Hamid