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
中科院分区:
文献类型:
--
作者:
Zizhuo Su;Rongjie Lin;Yuyang Chen;Xiaorong Shu;Haifeng Zhang;Shumin Liang;Ruqiong Nie;Jingfeng Wang;Shuanglun Xie
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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DOI:
10.1084/jem.20101174
发表时间:
2011-01-17
期刊:
The Journal of experimental medicine
影响因子:
--
作者:
Nigro P;Satoh K;O'Dell MR;Soe NN;Cui Z;Mohan A;Abe J;Alexis JD;Sparks JD;Berk BC
通讯作者:
Berk BC
影响因子:
4.8
作者:
Essler, M;Retzer, M;Siess, W
通讯作者:
Siess, W
影响因子:
9
作者:
通讯作者:
--
影响因子:
4
作者:
Woodsome, Terence P.;Polzin, Atsuko;Kitazawa, Toshio
通讯作者:
Kitazawa, Toshio
影响因子:
7
作者:
Fach, EM;Garulacan, LA;Opiteck, GJ
通讯作者:
Opiteck, GJ