Bradykinin increased the permeability of BTB via NOS/NO/ZONAB-mediating down-regulation of claudin-5 and occludin

Li-bo Liu; Xiao-bai Liu; Jun Ma; Yun-hui Liu; Zhi-qing Li; Teng Ma; Xi-he Zhao; Zhuo Xi; Yi-xue Xue

doi:10.1016/j.bbrc.2015.06.082

Bradykinin increased the permeability of BTB via NOS/NO/ZONAB-mediating down-regulation of claudin-5 and occludin

Biochem Biophys Res Commun. 2015 Aug 14;464(1):118-25. doi: 10.1016/j.bbrc.2015.06.082. Epub 2015 Jun 21.

Authors

Li-bo Liu¹, Xiao-bai Liu², Jun Ma¹, Yun-hui Liu³, Zhi-qing Li¹, Teng Ma¹, Xi-he Zhao¹, Zhuo Xi³, Yi-xue Xue⁴

Affiliations

¹ Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, PR China.
² The 96th Class, 7-Year Program, China Medical University, Shenyang 110122, PR China.
³ Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang 110004, PR China.
⁴ Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, PR China. Electronic address: [email protected].

PMID: 26106824
DOI: 10.1016/j.bbrc.2015.06.082

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.

Keywords: Blood-tumor barrier; Bradykinin; Claudin-5; NOS; Occludin; ZONAB.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood-Brain Barrier / drug effects
Bradykinin / pharmacology*
Brain Neoplasms / genetics
Brain Neoplasms / metabolism*
Brain Neoplasms / pathology
Claudin-5 / antagonists & inhibitors
Claudin-5 / genetics
Claudin-5 / metabolism
Enzyme Inhibitors / pharmacology
Female
Gene Expression Regulation, Neoplastic*
Glioma / genetics
Glioma / metabolism*
Glioma / pathology
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide / metabolism*
Nitric Oxide Synthase Type I / genetics
Nitric Oxide Synthase Type I / metabolism*
Nitric Oxide Synthase Type III / genetics
Nitric Oxide Synthase Type III / metabolism*
Occludin / antagonists & inhibitors
Occludin / genetics
Occludin / metabolism
Permeability / drug effects
Promoter Regions, Genetic
Protein Binding
Protein Transport
Rats
Rats, Wistar
Signal Transduction
Tight Junctions / drug effects
Tight Junctions / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism
Vasodilator Agents / pharmacology*

Substances

Claudin-5
Cldn5 protein, rat
Enzyme Inhibitors
Occludin
Ocln protein, rat
Transcription Factors
Vasodilator Agents
Nitric Oxide
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type III
Nos3 protein, rat
Bradykinin
NG-Nitroarginine Methyl Ester