Journal of Molecular Neuroscience

, Volume 46, Issue 1, pp 236–247

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

Authors

  • Hang Yu
    • Department of Neurobiology, College of Basic MedicineChina Medical University
    • Department of PhysiologyDaqing Branch of Haerbin Medical University
  • Ping Wang
    • Department of Neurobiology, College of Basic MedicineChina Medical University
    • Institute of Pathology and PathophysiologyChina Medical University
  • Ping An
    • Department of Neurobiology, College of Basic MedicineChina Medical University
    • Institute of Pathology and PathophysiologyChina Medical University
    • Department of Neurobiology, College of Basic MedicineChina Medical University
    • Institute of Pathology and PathophysiologyChina Medical University
Article

DOI: 10.1007/s12031-011-9584-5

Cite this article as:
Yu, H., Wang, P., An, P. et al. J Mol Neurosci (2012) 46: 236. doi:10.1007/s12031-011-9584-5

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.

Keywords

Angiopoietin-1Focal cerebral ischemia/reperfusionZO-1OccludinVE-cadherinPKCα

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

Copyright information

© Springer Science+Business Media, LLC 2011