Calcium-activated potassium channel activator down-regulated the expression of tight junction protein in brain tumor model in rats

Yan-ting Gu; Yi-xue Xue; Xiu-yan Wei; Hua Zhang; Yan Li

doi:10.1016/j.neulet.2011.02.029

Calcium-activated potassium channel activator down-regulated the expression of tight junction protein in brain tumor model in rats

Neurosci Lett. 2011 Apr 15;493(3):140-4. doi: 10.1016/j.neulet.2011.02.029. Epub 2011 Feb 18.

Authors

Yan-ting Gu¹, Yi-xue Xue, Xiu-yan Wei, Hua Zhang, Yan Li

Affiliation

¹ Department of Physiology, Life Science and Biology Pharmacopedia Institution, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning Province, PR China. yantinggu008@yahoo.com.cn

PMID: 21334421
DOI: 10.1016/j.neulet.2011.02.029

Abstract

This study was performed to investigate the mechanism of the blood-brain tumor-barrier (BTB) permeability increase, which was induced by NS1619, a selective K(Ca) channel activator. Using a rat brain glioma (C6) model, we exam the expression of ZO-1 and occludin in mRNA and protein level at different time point after intracarotid infusion of NS1619 (30 μg/kg/min) to tumor sites via RT-PCR and Western blot analysis. The mRNA and protein expression of ZO-1 and occludin had no great change before infusion and began to decrease significantly after 2 h NS1619 infusion, which was significantly attenuated by reactive oxygen species (ROS) scavenger (N-2-mercaptopropionyl glycine, MPG). In addition, MPG also significantly inhibited the increase of BTB permeability and malonaldehyde (MDA) level induced by NS1619. This led to the conclusion that NS1619 could time-dependently increase the BTB permeability by down-regulating the expression of tight junction protein, and this effect could be reversed by ROS.

Publication types

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

MeSH terms

Animals
Benzimidazoles / pharmacokinetics*
Benzimidazoles / therapeutic use
Blood-Brain Barrier / drug effects
Blood-Brain Barrier / metabolism
Blood-Brain Barrier / pathology
Brain Neoplasms / drug therapy
Brain Neoplasms / metabolism*
Brain Neoplasms / pathology
Cell Membrane Permeability / drug effects
Cell Membrane Permeability / genetics
Disease Models, Animal
Down-Regulation / drug effects
Down-Regulation / physiology*
Glioma / drug therapy
Glioma / metabolism*
Glioma / pathology
Male
Membrane Proteins / antagonists & inhibitors*
Membrane Proteins / biosynthesis
Membrane Proteins / genetics
Occludin
Phosphoproteins / biosynthesis
Potassium Channels, Calcium-Activated / agonists
Potassium Channels, Calcium-Activated / metabolism*
Rats
Rats, Wistar
Reactive Oxygen Species / metabolism
Tight Junctions / drug effects
Tight Junctions / metabolism*
Tight Junctions / pathology
Zonula Occludens-1 Protein

Substances

Benzimidazoles
Membrane Proteins
Occludin
Ocln protein, rat
Phosphoproteins
Potassium Channels, Calcium-Activated
Reactive Oxygen Species
Tjp1 protein, rat
Zonula Occludens-1 Protein
NS 1619