title: Recombinant human angiopoietin-1 ameliorates the expressions of ZO-1, occludin, VE-cadherin, and PKCα signaling after focal cerebral ischemia/reperfusion in rats.
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.
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, 110001, China; Department of Physiology, Daqing Branch of Haerbin Medical University, Daqing 163319, China. xueyixue888@yahoo.com.cn
authors.forename: Hang
authors.initials: H
authors.lastname: Yu
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: An
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
authors.forename: Xue
authors.initials: X
authors.lastname: Yixue
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D002545:Brain Ischemia / Q000378:metabolism*; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002199:Capillary Permeability / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008297:Male; D062793:Occludin / Q000096:biosynthesis / Q000235:genetics; D051571:Protein Kinase C-alpha / Q000096:biosynthesis / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D062826:Zonula Occludens-1 Protein / Q000096:biosynthesis / Q000235:genetics; D000099152:Cadherin 5
chemical_list: D042683:Angiopoietin-1; D015703:Antigens, CD; D015820:Cadherins; D062793:Occludin; D051571:Protein Kinase C-alpha; D011994:Recombinant Proteins; D062826:Zonula Occludens-1 Protein; D000099152:Cadherin 5; C467630:ANGPT1 protein, human; C568987:Ocln protein, rat; C569044:Tjp1 protein, rat