Article

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

  • Hang YuAffiliated withDepartment of Neurobiology, College of Basic Medicine, China Medical UniversityDepartment of Physiology, Daqing Branch of Haerbin Medical University
  • , Ping WangAffiliated withDepartment of Neurobiology, College of Basic Medicine, China Medical UniversityInstitute of Pathology and Pathophysiology, China Medical University
  • , Ping AnAffiliated withDepartment of Neurobiology, College of Basic Medicine, China Medical UniversityInstitute of Pathology and Pathophysiology, China Medical University
  • , Xue YixueAffiliated withDepartment of Neurobiology, College of Basic Medicine, China Medical UniversityInstitute of Pathology and Pathophysiology, China Medical University Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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-1 Focal cerebral ischemia/reperfusion ZO-1 Occludin VE-cadherin PKCα