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Recombinant Human Angiopoietin-1 Ameliorates the Expressions of ZO-1, Occludin, VE-cadherin, and PKCα Signaling after Focal Cerebral Ischemia/Reperfusion in Rats

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An Erratum to this article was published on 09 November 2011

Abstract

This study was performed to determine whether recombinant human angiopoietin-1 (Ang-1) decreases the permeability of the blood–brain barrier (BBB) in focal cerebral ischemia and reperfusion rats, whether Ang-1 opens the BBB by affecting tight junction associated proteins zonula occluden-1 (ZO-1), occludin and adherens junction protein vascular endothelial (VE)-cadherin, and whether the protein kinase C (PKC)α/myosin light chain (MLC) signaling pathway involves in it. The rats were divided into eight groups randomly: (1) sham-operated group, (2) ischemia group, (3–5) ischemia–reperfusion (middle cerebral artery occlusion and reperfusion (MCAO/R) 12 h, 48 h, and 7 days) and 0.9% saline groups, (6–8) ischemia–reperfusion (MCAO/R 12 h, 48 h, and 7 days) and Ang-1 groups. The BBB permeability was assessed by Evans blue extravasation. The messenger RNA and protein expressions of ZO-1, occludin, and VE-cadherin were determined by reverse transcription-polymerase chain reaction, western blot, and immunohistochemistry assays. The BBB permeability was significantly decreased after Ang-1 injection. The expressions of ZO-1, occludin, and VE-cadherin were increased after Ang-1 injection. These were in accordance with the results of immunohistochemistry assays. PKCα and phosphorylated MLC (p-MLC) expressions were decreased after Ang-1 injection. This study demonstrated that Ang-1 may decrease the permeability of BBB in MCAO/R rat by upregulation of ZO-1, occludin, and VE-cadherin. The decreased expressions of PKCα and p-MLC induced by Ang-1 also involved in this process.

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Abbreviations

BBB:

blood–brain barrier

Ang-1:

angiopoietin1

TJ:

tight junction

AJ:

adherens junctions

ZO-1:

zonula occludin 1

VE-cadherin:

vascular endothelial cadherin

MLC:

myosin light chain

p-MLC:

phosphorylated myosin light chain

TTC:

2,3,5-triphenyltetrazolium chloride

CCA:

common carotid artery

ICA:

internal carotid artery

ECA:

external carotid artery

MCAO:

middle cerebral artery occlusion

MCAO/R:

middle cerebral artery occlusion and reperfusion

PBS:

phosphate-buffered saline

Tris:

tris(hydroxymethyl) aminomethane

rCBF:

regional cerebral blood flow

RT-PCR:

reverse transcription polymerase chain reaction

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Acknowledgment

This work was supported by the Natural Science Foundation of China under contract no. 30800451, no. 30872656, no. 30700861, no. 30670723, and no. 30973079; Scientific and Technological Research Projects in Colleges and Universities of Liaoning Province, no. 2008850; the special fund for Scientific Research of Doctor-Degree Subjects in Colleges and Universities, no. 20092104110015; and Scientific and Technological Planning Projects of Shenyang, no. F10-205-1-37 and no. F10-205-1-22.

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Authors and Affiliations

  1. Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, 110001, China

    Hang Yu, Ping Wang, Ping An & Xue Yixue

  2. Department of Physiology, Daqing Branch of Haerbin Medical University, Daqing, 163319, China

    Hang Yu

  3. Institute of Pathology and Pathophysiology, China Medical University, Shenyang, 110004, China

    Ping Wang, Ping An & Xue Yixue

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  1. Hang Yu
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Correspondence to Xue Yixue.

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Hang Yu and Ping Wang have contributed equally to this work.

An erratum to this article can be found at http://dx.doi.org/10.1007/s12031-011-9666-4.

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Yu, H., Wang, P., An, P. et al. Recombinant Human Angiopoietin-1 Ameliorates the Expressions of ZO-1, Occludin, VE-cadherin, and PKCα Signaling after Focal Cerebral Ischemia/Reperfusion in Rats. J Mol Neurosci 46, 236–247 (2012). https://doi.org/10.1007/s12031-011-9584-5

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