The mechanism of the blood-brain tumor barrier permeability increase induced by minoxidil sulfate in a rat brain tumor model

Gu Yan-ting; Xue Yi-xue; Wang Yan-feng; ShangGuan QianRu; Lian Yan

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The mechanism of the blood-brain tumor barrier permeability increase induced by minoxidil sulfate in a rat brain tumor model

Gu Yan-ting 1 *,Xue Yi-xue 2,Wang Yan-feng 3,ShangGuan QianRu 1,Lian Yan 1 #

1.Departmen of Physiology, Life Science and Biology Pharmacopedia Institution, Shenyang Pharmaceutical University

2.Department of Neurobiology, College Basic of Medicine, China Medical University

3.Department of Orthopaedics, The First Affiliated Hospital, China Medical University

*Correspondence author

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Funding: Specialized Research Fund for the Doctoral Program of Higher Education （No.No. 20102134120007）, National Science fundation for China （No.No. 81201989, No. 81100924）, Doctor-beginning Science Foudation of Liaoning Province （No.No.2010119）

Opened online:20 December 2012

Accepted by: none

Citation: Gu Yan-ting,Xue Yi-xue,Wang Yan-feng.The mechanism of the blood-brain tumor barrier permeability increase induced by minoxidil sulfate in a rat brain tumor model[OL]. [20 December 2012] http://en.paper.edu.cn/en_releasepaper/content/4503754

Adenosine 5'-triphosphate-sensitive potassium channel (KATP channel) activator, minoxidil sulfate (MS), can selectively increase the permeability of the blood-tumor barrier (BTB); however, the mechanism by which this occurs is still under investigation. Using a rat brain glioma (C6) model, we examined the expression levels of occludin and claudin-5 at different time points after intracarotid infusion of MS (30 μg/kg/min) by western blotting. The protein expression levels of occludin and claudin-5 showed no changes after 1 hour and began to decrease significantly after 2 hours of MS infusion, accompanied by tight junction (TJ) opening. The reactive oxygen species (ROS) scavenger, N-2-mercaptopropionyl glycine (MPG), significantly attenuated the MS-induced BTB permeability increases. In the in vitro co-culture of brain microvascular endothelial cells (BMECs) with C6 glioma cells, MS induced a time-dependent increase in ROS production which reached its maximum peak at 2 hours post incubation (100 μmol/ml), as determined by DHE fluorescence measurements. Taken together, all of these results suggested that MS might increase BTB permeability in a time-dependent manner by down-regulating TJ protein expression and this effect could be reversed by the ROS scavenger, MPG.

Keywords:Blood-tumor barrier; ATP-sensitive potassium channel; Glioma; Reactive oxygen species; Tight junction protein

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