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高胆固醇血症血清通过紧密连接蛋白-1和磷脂酰肌醇3-激酶信号通路增加内皮细胞的通透性。

Hypercholesterolaemic serum increases the permeability of endothelial cells through zonula occludens-1 with phosphatidylinositol 3-kinase signaling pathway.

作者信息

Bian Chang, Xu Geng, Wang Jianan, Ma Ji, Xiang Meixiang, Chen Peng

机构信息

Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.

出版信息

J Biomed Biotechnol. 2009;2009:814979. doi: 10.1155/2009/814979. Epub 2010 Jan 27.

DOI:10.1155/2009/814979
PMID:20150971
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2817810/
Abstract

PURPOSE

Hypercholesterolemia and tight junctions play important roles in atherosclerosis. But the relationship between these two factors is unclear. In the present study, we investigated whether hypercholesterolemic serum could change the permeability of endothelial cells through altering expression and/or distribution of tight junction protein zonula occludens-1 (ZO-1). Phosphatidylinositol 3-kinase (PI3K) signaling pathway was also examined.

MATERIALS AND METHODS

Cultured endothelial cells were treated with different concentration levels of hypercholesterolemic serum. The expression and distribution of ZO-1, the permeability of cultured cells and the involvement of PI3K signaling pathway were measured by various methods.

RESULTS

In the present study, we found that hypercholesterolemic serum could not change the expression of ZO-1 either in mRNA or protein level. However, hypercholesterolemic serum could change the distribution of ZO-1 in cultured endothelial cells, and increase the permeability with a dose-dependent manner. When PI3K specific inhibitor wortmannin was used, the effects induced by hypercholesterolemic serum could be partly reversed. The role of PI3K signaling pathway was further confirmed by PI3K activity assay.

CONCLUSIONS

Our results suggested that although hypercholesterolemic serum could not change the expression of ZO-1, it could change the distribution and increase the permeability in endothelial cells through PI3K signaling pathway.

摘要

目的

高胆固醇血症和紧密连接在动脉粥样硬化中起重要作用。但这两个因素之间的关系尚不清楚。在本研究中，我们调查了高胆固醇血症血清是否能通过改变紧密连接蛋白闭合蛋白-1（ZO-1）的表达和/或分布来改变内皮细胞的通透性。同时也检测了磷脂酰肌醇3-激酶（PI3K）信号通路。

材料与方法

用不同浓度的高胆固醇血症血清处理培养的内皮细胞。通过多种方法检测ZO-1的表达和分布、培养细胞的通透性以及PI3K信号通路的参与情况。

结果

在本研究中，我们发现高胆固醇血症血清在mRNA或蛋白质水平上均不能改变ZO-1的表达。然而，高胆固醇血症血清可改变培养的内皮细胞中ZO-1的分布，并以剂量依赖的方式增加通透性。当使用PI3K特异性抑制剂渥曼青霉素时，高胆固醇血症血清诱导的效应可部分逆转。PI3K活性测定进一步证实了PI3K信号通路的作用。

结论

我们的结果表明，虽然高胆固醇血症血清不能改变ZO-1的表达，但它可通过PI3K信号通路改变内皮细胞中ZO-1的分布并增加其通透性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6317/2817810/99025e3165b5/JBB2009-814979.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6317/2817810/1a114006d8c6/JBB2009-814979.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6317/2817810/86cf7db31140/JBB2009-814979.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6317/2817810/0167c258158a/JBB2009-814979.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6317/2817810/99025e3165b5/JBB2009-814979.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6317/2817810/1a114006d8c6/JBB2009-814979.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6317/2817810/86cf7db31140/JBB2009-814979.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6317/2817810/0167c258158a/JBB2009-814979.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6317/2817810/99025e3165b5/JBB2009-814979.004.jpg

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