title: Calcium-activated potassium channel activator down-regulated the expression of tight junction protein in brain tumor model in rats.
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.
authors.affiliation: Department of Physiology, Life Science and Biology Pharmacopedia Institution, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning Province, PR China. yantinggu008@yahoo.com.cn
authors.forename: Yan-ting
authors.initials: YT
authors.lastname: Gu
authors.forename: Yi-xue
authors.initials: YX
authors.lastname: Xue
authors.forename: Xiu-yan
authors.initials: XY
authors.lastname: Wei
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D062793:Occludin; D010750:Phosphoproteins / Q000096:biosynthesis; D024681:Potassium Channels, Calcium-Activated / Q000819:agonists / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D062826:Zonula Occludens-1 Protein
chemical_list: D001562:Benzimidazoles; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; D024681:Potassium Channels, Calcium-Activated; D017382:Reactive Oxygen Species; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C086491:NS 1619