Alterations in function and expression of ABC transporters at blood-brain barrier under diabetes and the clinical significances

Li Liu,Xiao-Dong Liu

doi:10.3389/fphar.2014.00273

Abstract

Diabetes is a systematic metabolic disease, which often develops a number of well-recognized vascular complications including brain complications which may partly result from the dysfunction of blood-brain barrier (BBB). BBB is generally considered as a mechanism for protecting the brain from unwanted actions resulting from substances in the blood and maintaining brain homeostasis via monitoring the entry or efflux of compounds. ATP-binding cassette (ABC) family of transporters including P-glycoprotein (P-GP) and breast cancer-related protein (BCRP), widely expressed in the luminal membrane of the microvessel endothelium and in the apical membrane of the choroids plexus epithelium, play important roles in the function of BBB. However, these transporters are easily altered by some diseases. The present article was focused on the alteration in expression and function of both P-GP and BCRP at BBB by diabetes and the clinical significances.

Highlights

The blood-brain barrier (BBB) is a multicellular vascular structure that separates the central nervous system (CNS) from the peripheral blood circulation
Alterations of ATP-binding cassette (ABC) transporters under diabetes membrane localization is certain for P-glycoprotein (ABCB1), Multidrug Resistance-Associated Protein 2, MRP2 (ABCC2), and breast cancer resistance protein (ABCG2) (BCRP)
P-GP AND DIABETES Diabetes is often associated with disorder of energy metabolism and increases of pro-inflammatory cytokines in the systemic circulation, which inferred that diabetes may alter expression and function of ABC transporters at BBB, in turn, affect BBB permeability

Summary

INTRODUCTION

The blood-brain barrier (BBB) is a multicellular vascular structure that separates the central nervous system (CNS) from the peripheral blood circulation. ATP-binding cassette (ABC) efflux transporters on the other hand extrude metabolic wastes into the blood and form a selective, active barrier protecting the CNS by limiting xenobiotics, including toxins and a large number of drugs, from entering the brain (Hartz and Bauer, 2011). Three ABC subfamilies, B, C, and G, contain transporters that function as multispecific, ATP-driven efflux pumps, and largely handle foreign chemicals (xenobiotics) As a rule, these ABC transporters are expressed in all cells, but they are most highly expressed in barrier (such as the BBB) and excretory tissues. Functional studies with wild-type and knock-out rodents as well as immunohistochemistry indicate that luminal www.frontiersin.org

Liu and Liu

ALTERATION IN BBB PERMEABILITY BY DIABETES

Findings

ABC TRANSPORTERS AT BBB AND DIABETES