Role of VPO1, a newly identified heme-containing peroxidase, in ox-LDL induced endothelial cell apoptosis.
Role of VPO1, a newly identified heme-containing peroxidase, in ox-LDL induced endothelial cell apoptosis.
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VPO1（一种新发现的含血红素过氧化物酶）在 ox-LDL 诱导的内皮细胞凋亡中的作用。
DOI：
10.1016/j.freeradbiomed.2011.07.004
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发表时间：
2011-10-15
影响因子：
7.4
通讯作者：
Zhang, Guo-Gang
中科院分区：
文献类型：
--
作者：
Bai, Yong-Ping;Hu, Chang-Ping;Yuan, Qiong;Peng, Jun;Shi, Rui-Zheng;Yang, Tian-Lun;Cao, Ze-Hong;Li, Yuan-Jian;Cheng, Guangjie;Zhang, Guo-Gang
髓过氧化物酶（MPO）是参与动脉粥样硬化发生发展的重要酶。血管过氧化物酶1（Vascular peroxidase 1，VPO 1）是新近发现的过氧化物酶家族成员，主要表达于血管内皮细胞和平滑肌细胞，具有与MPO相似的结构特征和生物学活性。本研究旨在探讨VPO 1对氧化型低密度脂蛋白（ox-LDL）诱导的内皮细胞凋亡的影响及其机制。结果显示，ox-LDL可诱导内皮细胞凋亡，并呈浓度和时间依赖性地诱导VPO 1的表达，同时伴随细胞内活性氧（ROS）和次氯酸（HOCl）的产生，以及NADPH氧化酶gp 91 phox亚基蛋白表达和p38 MAPK磷酸化的上调。氧化型低密度脂蛋白的所有这些作用都被VPO 1基因沉默和NADPH氧化酶gp 91 phox亚基基因沉默或用NADPH氧化酶抑制剂夹竹桃苷或二苯基碘鎓预处理所抑制。p38 MAPK抑制剂SB 203580或caspase-3抑制剂DEVD-CHO可显著抑制ox-LDL诱导的内皮细胞凋亡，但对细胞内ROS和HOCl的产生以及NADPH氧化酶gp 91 phox亚基和VPO 1的表达无影响。总的来说，这些研究结果首次表明，VPO 1在ox-LDL诱导的内皮细胞凋亡中起着关键作用，并且VPO 1/HOCl与现在公认的NADPH氧化酶/ROS/p38 MAPK/caspase-3途径参与ox-LDL诱导的内皮细胞凋亡的教条之间存在正反馈回路。
Myeloperoxidase (MPO) is an important enzyme involved in the genesis and development of atherosclerosis. Vascular peroxidase 1 (VPO1) is a newly discovered member of the peroxidase family that is mainly expressed in vascular endothelial cells and smooth muscle cells and has structural characteristics and biological activity similar to those of MPO. Our specific aims were to explore the effects of VPO1 on endothelial cell apoptosis induced by oxidized low-density lipoprotein (ox-LDL) and the underlying mechanisms. The results showed that ox-LDL induced endothelial cell apoptosis and the expression of VPO1 in endothelial cells in a concentration- and time-dependent manner concomitant with increased intracellular reactive oxygen species (ROS) and hypochlorous acid (HOCl) generation, and up-regulated protein expression of the NADPH oxidase gp91phox subunit and phosphorylation of p38 MAPK. All these effects of ox-LDL were inhibited by VPO1 gene silencing and NADPH oxidase gp91phox subunit gene silencing or by pretreatment with the NADPH oxidase inhibitor apocynin or diphenyliodonium. The p38 MAPK inhibitor SB203580 or the caspase-3 inhibitor DEVD-CHO significantly inhibited ox-LDL-induced endothelial cell apoptosis, but had no effect on intracellular ROS and HOCl generation or the expression of NADPH oxidase gp91phox subunit or VPO1. Collectively, these findings suggest for the first time that VPO1 plays a critical role in ox-LDL-induced endothelial cell apoptosis and that there is a positive feedback loop between VPO1/HOCl and the now-accepted dogma that the NADPH oxidase/ROS/p38 MAPK/caspase-3 pathway is involved in ox-LDL-induced endothelial cell apoptosis.
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影响因子：
6.6
作者：
Frey RS;Ushio-Fukai M;Malik AB
通讯作者：
Malik AB
影响因子：
37.8
作者：
LIBBY, P
通讯作者：
LIBBY, P
影响因子：
3.9
作者：
Kumar, AP;Ryan, C;Reynolds, WF
通讯作者：
Reynolds, WF
DOI：
10.1152/ajpgi.1998.275.4.g749
发表时间：
1998-10-01
影响因子：
4.5
作者：
Celli, A;Que, FG;LaRusso, NF
通讯作者：
LaRusso, NF
影响因子：
3.9
作者：
Dworakowski, R.;Anilkumar, N.;Shah, A. M.
通讯作者：
Shah, A. M.