title: Bradykinin increased the permeability of BTB via NOS/NO/ZONAB-mediating down-regulation of claudin-5 and occludin.
abstract: After demonstrating bradykinin (BK) could increase the permeability of blood-tumor barrier (BTB) via opening the tight junction (TJ), and that the possible mechanism is unclear, we demonstrated that BK could increase the expressions of eNOS and nNOS and promote ZONAB translocation into nucleus. NOS inhibitors l-NAME and 7-NI could effectively block the effect of BK on increasing BTB permeability, decreasing the expressions of claudin-5 and occludin and promoting the translocation of ZONAB. Overexpression of ZONAB could significantly enhance BK-mediating BTB permeability. Meanwhile, chromatin immunoprecipitation verified ZONAB interacted with the promoter of claudin-5 and occludin respectively. This study indicated NOS/NO/ZONAB pathway might be involved in BK's increasing the permeability of BTB.
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, PR China.
authors.forename: Li-bo
authors.initials: LB
authors.lastname: Liu
authors.affiliation: The 96th Class, 7-Year Program, China Medical University, Shenyang 110122, PR China.
authors.forename: Xiao-bai
authors.initials: XB
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang 110004, PR China.
authors.forename: Yun-hui
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, PR China.
authors.forename: Zhi-qing
authors.initials: ZQ
authors.lastname: Li
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, PR China.
authors.forename: Teng
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, PR China.
authors.forename: Xi-he
authors.initials: XH
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang 110004, PR China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Xi
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, PR China. Electronic address: xueyixue888@163.com.
authors.forename: Yi-xue
authors.initials: YX
authors.lastname: Xue
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D062507:Claudin-5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D062793:Occludin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D062507:Claudin-5; C491510:Cldn5 protein, rat; D004791:Enzyme Inhibitors; D062793:Occludin; C568987:Ocln protein, rat; D014157:Transcription Factors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester
keywords: Blood-tumor barrier; Bradykinin; Claudin-5; NOS; Occludin; ZONAB