Mechanism of thioflavin T accumulation inside cells overexpressing P-glycoprotein or multidrug resistance-associated protein: Role of lipophilicity and positive charge

被引：37

作者：

Darghal, N

Garnier-Suillerot, A

Salerno, M

机构：

[1] Univ Paris 13, CNRS, Lab Biophys Mol Cellulaire & Tissulaire, UMR 7033, F-93017 Bobigny, France

[2] Univ Paris 06, F-93017 Bobigny, France

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2006年 / 343卷 / 02期

关键词：

Alzheimer; blood-brain barrier; thioflavin T; beta-amyloid; P-glycoprotein; MRP1;

D O I：

10.1016/j.bbrc.2006.03.024

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Alzheimer's disease is characterized by the presence of amyloid deposition. Thioflavin T (ThT) has been one of the molecules of choice to attempt the detection of these amyloid deposits. However, it has been reported that ThT was unable to cross blood-brain barrier (BBB). Our aim was to understand the mechanism according to which it has been said that ThT is not able to cross the BBB. For this purpose we have used cellular models overexpressing P-glycoprotein (P-gp) or multidrug resistance-associated protein (MRP1), two proteins overexpressed in BBB. Our results show that: (i) ThT is able to cross membranes and to penetrate inside the cells; (ii) ThT is a P-gp substrate; (iii) ThT is poor MRP1 substrate. In conclusion, our results suggest that two factors could be involved in the low accumulation of ThT in the brain: ThT is a P-gp substrate and its lipophilicity is low. (c) 2006 Elsevier Inc. All rights reserved.

引用

页码：623 / 629

页数：7

共 30 条

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