Oxidized Low-Density Lipoprotein-Induced Cyclophilin A Secretion Requires ROCK-Dependent Diphosphorylation of Myosin Light Chain

Oxidized Low-Density Lipoprotein-Induced Cyclophilin A Secretion Requires ROCK-Dependent Diphosphorylation of Myosin Light Chain
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氧化低密度脂蛋白诱导的亲环蛋白 A 分泌需要肌球蛋白轻链的 ROCK 依赖性二磷酸化

DOI:
10.1159/000449387
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发表时间:
2016-11
影响因子:
1.7
通讯作者:
Shuanglun Xie
Shuanglun Xie
中科院分区:
医学4区
文献类型:
--
作者:
Zizhuo Su;Rongjie Lin;Yuyang Chen;Xiaorong Shu;Haifeng Zhang;Shumin Liang;Ruqiong Nie;Jingfeng Wang;Shuanglun Xie

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目的:人们认为亲环素A(CyPA)在动脉粥样硬化斑块内的积聚与动脉粥样硬化的进展有关。然而,动脉粥样硬化斑块内CyPA的来源仍不清楚。本研究旨在检测……(原文此处“dete”表述不完整,推测是“detect”,完整翻译需结合完整内容)
Objective: Accumulation of cyclophilin A (CyPA) within atherosclerotic lesions is thought to be implicated in the progression of atherosclerosis. However, the source of CyPA within atherosclerotic lesions is still unknown. The aim of this study is to determine the role of oxidized low-density lipoproteins (ox-LDL) in vascular smooth muscle cell (VSMC)-derived CyPA secretion and the underlying mechanism. Methods and Results: Abundant CyPA and α-smooth muscle actin (α-SMA) expressed in atherosclerotic lesions was observed in apolipoprotein E-deficient mice. ox-LDL induced CyPA secretion from a primary culture of rat aortic smooth muscle cells in a dose- and time-dependent manner. Sulfosuccinimidyloleate, a CD36 inhibitor, prevented the ox-LDL-induced CyPA secretion. Pre-exposure to either the actin-depolymerizing agent cytochalasin D or the actin-polymerizing agent jasplakinolide inhibited CyPA secretion induced by ox-LDL. Gene silencing of vesicle-associated membrane protein 2 suppressed ox-LDL-induced CyPA secretion. ox-LDL caused the phosphorylation of myosin light chain (MLC). Inhibition of MLC by blebbistatin reversed the secretion of CyPA and the phosphorylation of MLC induced by ox-LDL. MLC kinase inhibitor ML-7 reduced the monophosphorylation of MLC but did not reduce CyPA secretion. Pretreatment with the rho-associated coiled-coil kinase (ROCK) inhibitor Y27632 blocked diphosphorylation of MLC and secretion of CyPA induced by ox-LDL. Conclusions: ox-LDL-induced CyPA secretion requires vesicle transportation, actin remodeling and ROCK-dependent diphosphorylation of MLC. VSMC-derived CyPA induced by ox-LDL may be associated with increased CyPA expression in atherosclerotic lesions.
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