title: Mechanisms for endothelial monocyte-activating polypeptide-II-induced opening of the blood-tumor barrier.
abstract: Endothelial monocyte-activating polypeptide-II (EMAP-II) increases blood-tumor barrier (BTB) permeability by inducing alterations in the tight junction (TJ) complex between brain endothelial cells. In the present study, an in vitro BTB model was used to search for the interacting and functional cell surface molecule of EMAP-II as well as the signaling pathway involved in the EMAP-II-induced BTB hyperpermeability. Our results revealed that EMAP-II-induced increase in BTB permeability and down-regulation of TJ-related proteins occludin and ZO-1 were associated with its binding to ATP synthase α subunit (α-ATP synthase) on the surface of rat brain microvascular endothelial cells (BMECs). In addition, we observed that EMAP-II administration activated protein kinase C (PKC) and induced the translocation of PKC from the cytosolic to the membrane fraction of BMECs. The effects of EMAP-II on BTB permeability as well as expression levels of occludin and ZO-1 in BMECs were significantly diminished by H7, the inhibitor of PKC. In summary, these data suggest that EMAP-II increases BTB permeability through α-ATP synthase on the surface of BMECs, and PKC signaling pathway might be involved in this process.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, 110004, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Yun-hui
authors.initials: YH
authors.lastname: Liu
authors.forename: Yi-xue
authors.initials: YX
authors.lastname: Xue
authors.forename: Li-bo
authors.initials: LB
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000473:pathology / Q000502:physiology*; D001932:Brain Neoplasms / Q000098:blood supply* / Q000378:metabolism; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D005910:Glioma / Q000098:blood supply / Q000378:metabolism; D009363:Neoplasm Proteins / Q000502:physiology*; D061251:Primary Cell Culture; D016601:RNA-Binding Proteins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016207:Cytokines; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1