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

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 lipopr... Full description

Journal Title: Journal of vascular research 2016-12, Vol.53 (3-4), p.206-215
Main Author: Su, Zizhuo
Other Authors: Lin, Rongjie , Chen, Yuyang , Shu, Xiaorong , Zhang, Haifeng , Liang, Shumin , Nie, Ruqiong , Wang, Jingfeng , Xie, Shuanglun
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: Basel, Switzerland: S. Karger AG
ID: ISSN: 1018-1172
Link: https://www.ncbi.nlm.nih.gov/pubmed/27825172
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recordid: cdi_crossref_primary_10_1159_000449387
title: Oxidized Low-Density Lipoprotein-Induced Cyclophilin A Secretion Requires ROCK-Dependent Diphosphorylation of Myosin Light Chain
format: Article
creator:
  • Su, Zizhuo
  • Lin, Rongjie
  • Chen, Yuyang
  • Shu, Xiaorong
  • Zhang, Haifeng
  • Liang, Shumin
  • Nie, Ruqiong
  • Wang, Jingfeng
  • Xie, Shuanglun
subjects:
  • Actin
  • Actins - metabolism
  • Animals
  • Aorta - enzymology
  • Aorta - pathology
  • Aorta - secretion
  • Aortic Diseases - enzymology
  • Aortic Diseases - genetics
  • Aortic Diseases - pathology
  • Apolipoproteins
  • Apolipoproteins E - deficiency
  • Apolipoproteins E - genetics
  • Atherosclerosis
  • Atherosclerosis - enzymology
  • Atherosclerosis - genetics
  • Atherosclerosis - pathology
  • Blood lipids
  • CD36 Antigens - metabolism
  • Cells, Cultured
  • Cyclophilin A - secretion
  • Diet, High-Fat
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Genetic engineering
  • Lipoproteins, LDL - pharmacology
  • Low density lipoproteins
  • Male
  • Mice, Knockout
  • Muscle proteins
  • Muscle, Smooth, Vascular - drug effects
  • Muscle, Smooth, Vascular - enzymology
  • Muscle, Smooth, Vascular - secretion
  • Myocytes, Smooth Muscle - drug effects
  • Myocytes, Smooth Muscle - enzymology
  • Myocytes, Smooth Muscle - secretion
  • Myosin
  • Myosin Light Chains - metabolism
  • Phosphorylation
  • Rats
  • Research Paper
  • rho-Associated Kinases - metabolism
  • RNA Interference
  • Time Factors
  • Transfection
ispartof: Journal of vascular research, 2016-12, Vol.53 (3-4), p.206-215
description: 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.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 1018-1172
fulltext: fulltext
issn:
  • 1018-1172
  • 1423-0135
url: Link


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titleOxidized Low-Density Lipoprotein-Induced Cyclophilin A Secretion Requires ROCK-Dependent Diphosphorylation of Myosin Light Chain
sourceAlma/SFX Local Collection
creatorSu, Zizhuo ; Lin, Rongjie ; Chen, Yuyang ; Shu, Xiaorong ; Zhang, Haifeng ; Liang, Shumin ; Nie, Ruqiong ; Wang, Jingfeng ; Xie, Shuanglun
creatorcontribSu, Zizhuo ; Lin, Rongjie ; Chen, Yuyang ; Shu, Xiaorong ; Zhang, Haifeng ; Liang, Shumin ; Nie, Ruqiong ; Wang, Jingfeng ; Xie, Shuanglun
descriptionObjective: 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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languageeng
publisherBasel, Switzerland: S. Karger AG
subjectActin ; Actins - metabolism ; Animals ; Aorta - enzymology ; Aorta - pathology ; Aorta - secretion ; Aortic Diseases - enzymology ; Aortic Diseases - genetics ; Aortic Diseases - pathology ; Apolipoproteins ; Apolipoproteins E - deficiency ; Apolipoproteins E - genetics ; Atherosclerosis ; Atherosclerosis - enzymology ; Atherosclerosis - genetics ; Atherosclerosis - pathology ; Blood lipids ; CD36 Antigens - metabolism ; Cells, Cultured ; Cyclophilin A - secretion ; Diet, High-Fat ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Genetic engineering ; Lipoproteins, LDL - pharmacology ; Low density lipoproteins ; Male ; Mice, Knockout ; Muscle proteins ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - enzymology ; Muscle, Smooth, Vascular - secretion ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - enzymology ; Myocytes, Smooth Muscle - secretion ; Myosin ; Myosin Light Chains - metabolism ; Phosphorylation ; Rats ; Research Paper ; rho-Associated Kinases - metabolism ; RNA Interference ; Time Factors ; Transfection
ispartofJournal of vascular research, 2016-12, Vol.53 (3-4), p.206-215
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0Su, Zizhuo
1Lin, Rongjie
2Chen, Yuyang
3Shu, Xiaorong
4Zhang, Haifeng
5Liang, Shumin
6Nie, Ruqiong
7Wang, Jingfeng
8Xie, Shuanglun
title
0Oxidized Low-Density Lipoprotein-Induced Cyclophilin A Secretion Requires ROCK-Dependent Diphosphorylation of Myosin Light Chain
1Journal of vascular research
addtitleJ Vasc Res
descriptionObjective: 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.
subject
0Actin
1Actins - metabolism
2Animals
3Aorta - enzymology
4Aorta - pathology
5Aorta - secretion
6Aortic Diseases - enzymology
7Aortic Diseases - genetics
8Aortic Diseases - pathology
9Apolipoproteins
10Apolipoproteins E - deficiency
11Apolipoproteins E - genetics
12Atherosclerosis
13Atherosclerosis - enzymology
14Atherosclerosis - genetics
15Atherosclerosis - pathology
16Blood lipids
17CD36 Antigens - metabolism
18Cells, Cultured
19Cyclophilin A - secretion
20Diet, High-Fat
21Disease Models, Animal
22Dose-Response Relationship, Drug
23Genetic engineering
24Lipoproteins, LDL - pharmacology
25Low density lipoproteins
26Male
27Mice, Knockout
28Muscle proteins
29Muscle, Smooth, Vascular - drug effects
30Muscle, Smooth, Vascular - enzymology
31Muscle, Smooth, Vascular - secretion
32Myocytes, Smooth Muscle - drug effects
33Myocytes, Smooth Muscle - enzymology
34Myocytes, Smooth Muscle - secretion
35Myosin
36Myosin Light Chains - metabolism
37Phosphorylation
38Rats
39Research Paper
40rho-Associated Kinases - metabolism
41RNA Interference
42Time Factors
43Transfection
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7Wang, Jingfeng
8Xie, Shuanglun
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titleOxidized Low-Density Lipoprotein-Induced Cyclophilin A Secretion Requires ROCK-Dependent Diphosphorylation of Myosin Light Chain
authorSu, Zizhuo ; Lin, Rongjie ; Chen, Yuyang ; Shu, Xiaorong ; Zhang, Haifeng ; Liang, Shumin ; Nie, Ruqiong ; Wang, Jingfeng ; Xie, Shuanglun
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1Actins - metabolism
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10Apolipoproteins E - deficiency
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13Atherosclerosis - enzymology
14Atherosclerosis - genetics
15Atherosclerosis - pathology
16Blood lipids
17CD36 Antigens - metabolism
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30Muscle, Smooth, Vascular - enzymology
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38Rats
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40rho-Associated Kinases - metabolism
41RNA Interference
42Time Factors
43Transfection
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abstractObjective: 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.
copBasel, Switzerland
pubS. Karger AG
pmid27825172
doi10.1159/000449387
tpages10
oafree_for_read