title: Role of RhoA/ROCK signaling in endothelial-monocyte-activating polypeptide II opening of the blood-tumor barrier: role of RhoA/ROCK signaling in EMAP II opening of the BTB.
abstract: The purpose of the present study was to determine the potential for RhoA/ROCK signaling to play a role in endothelial-monocyte-activating polypeptide (EMAP) II-induced increase in blood-tumor barrier (BTB) permeability in rat brain microvascular endothelial cells (RBMECs). In the present study, we used an in vitro BTB model, a RhoA inhibitor (C3 exoenzyme) and a ROCK inhibitor (Y27632) to determine whether RhoA/ROCK pathway play a role in the process of TJ disassembly, stress fiber formation, MLC and cofilin phosphorylation, as well as increase of BTB permeability induced by EMAP II. The results revealed that BTB permeability was increased by EMAP II induction, and C3 exoenzyme or Y27632 could partially inhibit the EMAP II-induced increase of BTB permeability. The significant down-regulations in tight junction (TJ)-associated proteins occludin, claudin-5 and ZO-1 and stress fiber formation by EMAP II administration were observed, which were partly prevented by C3 exoenzyme or Y27632 pretreatment. Moreover, the significant increases in RhoA activity, myosin light chain (MLC) and cofilin phosphorylation by EMAP II administration were observed, MLC and cofilin phosphorylation were partly inhibited by C3 exoenzyme or Y27632 pretreatment. The present study demonstrates that the activation of RhoA/ROCK signaling in RBMECs was required for the increase of BTB permeability and these effects are related with the ability for RhoA/ROCK to mediate TJ disassembly and stress fiber formation by phosphorylating cofilin and MLC.
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, People's Republic of China, 110001.
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Yi-Xue
authors.initials: YX
authors.lastname: Xue
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Liu
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology; D005910:Glioma / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D019108:Tight Junctions / Q000201:enzymology / Q000473:pathology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology*
chemical_list: C485473:Eml2 protein, rat; D008869:Microtubule-Associated Proteins; C578418:ROCK1 protein, rat; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein