Chromogranin A derived peptide CGA47-66 suppresses hyperpermeability of immortalized brain microvascular endothelial cells induced by lipopolysaccharide

Siyi LIU; Yan ZENG; Shuke LIU; Fu WEI; Shan XU; Dan ZHANG

doi:10.16016/j.1000-5404.201801036

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Chromogranin A derived peptide CGA47-66 suppresses hyperpermeability of immortalized brain microvascular endothelial cells induced by lipopolysaccharide

Basic Medicine | 更新时间：2026-01-09

- Chromogranin A derived peptide CGA47-66 suppresses hyperpermeability of immortalized brain microvascular endothelial cells induced by lipopolysaccharide
- Journal of Third Military Medical University Vol. 40, Issue 15, Pages: 1364-1369(2018)
- 作者机构：
  
  400016 重庆, 重庆医科大学附属第一医院重症医学科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81071531);the General Program of National Natural Science Foundation of China(81372102);the General Program of Natural Science Foundation of Chongqing(CSTC2009BB5066)
- DOI：10.16016/j.1000-5404.201801036
  CLC： R322.13;R329.27;R341
- Received：04 January 2018，
  
  Revised：2018-02-02，
  
  Published：15 August 2018
- 稿件说明：
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Siyi LIU, Yan ZENG, Shuke LIU, et al. Chromogranin A derived peptide CGA47-66 suppresses hyperpermeability of immortalized brain microvascular endothelial cells induced by lipopolysaccharide[J]. Journal of Third Military Medical University, 2018, 40(15): 1364-1369.
DOI：

Siyi LIU, Yan ZENG, Shuke LIU, et al. Chromogranin A derived peptide CGA47-66 suppresses hyperpermeability of immortalized brain microvascular endothelial cells induced by lipopolysaccharide[J]. Journal of Third Military Medical University, 2018, 40(15): 1364-1369. DOI： 10.16016/j.1000-5404.201801036.

摘要

目的

探讨嗜铬粒蛋白A衍生多肽CHR（chromofungin）对LPS所诱导的永生化人脑微血管内皮细胞高通透性的影响。

方法

分别用LPS、CHR、CGA

4-16

作用于人脑微血管内皮细胞（human brain microvascular endothelial cells，HBMEC），用CCK8法检测不同浓度LPS刺激HBMEC细胞活力变化；EVOM法及Transwell小室法检测内皮细胞相对通透性；Western blot及RT-PCR法检测紧密连接蛋白（ZO-1和Claudin-5）的表达情况。

结果

与空白组相比，随着LPS浓度增加，HBMEC细胞的活性受到显著抑制（

0.05）。随着LPS作用时间延长，其细胞内紧密连接蛋白ZO-1、Claudin-5的表达逐渐下调，6 h后蛋白表达量降到最低（

0.05），12 h和24 h后其蛋白表达与6 h相比无明显差异。LPS作用下HBMEC单层细胞电阻值明显降低（

=-18.214，

0.001），细胞通透性显著升高（

=6.083，

=0.004），ZO-1、Claudin-5的蛋白和mRNA表达明显下调（

0.05），而CHR可显著改善上述变化。

结论

嗜铬粒蛋白A衍生多肽CHR能通过上调紧密连接相关蛋白的表达从而改善LPS所致的脑微血管内皮细胞高通透性。

Abstract

Objective

To determine the effect of chromogranin A derived peptide CGA47-66 (chromofungin

CHR) on lipopolysaccharide (LPS) induced high permeability of immortalized brain microvascular endothelial cells.

Methods

Immortalized human brain microvascular endothelial cells (HBMEC) were exposed to LPS

CHR and CGA4-16 respectively. Cell counting kit-8 (CCK8) assay was used to detect the cell viability after inducement of different concentrations of LPS. The relative permeability of HBMEC cells was measured by a Transwell chamber system and epithelial voltmeter (EVOM). The expression levels of the tight junction protein ZO-1 and Claudin-5 were detected by Western blotting and quantitative real-time polymerase chain reaction (RT-PCR).

Results

Compared with the blank control cells

the viability of HBMEC cells was significantly inhibited with the increase concentrations of LPS (

0.05). With the elapse of time

LPS treatment decreased the expression levels of ZO-1 and Claudin-5 gradually

and the levels reached the lowest after 6 h (

0.05)

which having no significant difference with the levels at 12 or 24 h. LPS treatment also resulted in significantly decreased transendothelial electrical resistance (

=-18.214

0.001)

increased cell permeability (

=6.083

=0.004)

and down-regulation of ZO-1 and Claudin-5 at mRNA and protein levels (

0.05). However

CHR significantly attenuated the above changes.

Conclusion

CHR could attenuate the hyperperneability of human brain microvascular endothelial cells induced by LPS through up-regulating tight junction proteins.

关键词

Keywords

references

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