A new multidrug resistance protein at the blood-brain barrier.
Porcine brain capillary endothelial cells (PBCEC) cultured in serum-free and hydrocortisone supplemented medium are characterised by high transendothelial electrical resistances and low cell monolayer permeabilities for small solutes very similar to the blood-brain barrier (BBB) in vivo. Differential screening of a subtracted cDNA library disclosed a 2.1-kb mRNA that is overexpressed in hydrocortisone treated PBCEC relative to untreated cells. The mRNA encodes a 656-aa member of the ATP-binding cassette (ABC) superfamily of transporters that we named brain multidrug resistance protein (BMDP). Phylogenetic analysis and multiple sequence alignment showed that porcine BMDP is most related to the human and mouse breast cancer resistance protein (BCRP). Northern blot analysis revealed that BMDP is expressed in brain tissue in vivo and was predominantly localised within the endothelial cells isolated from brain capillaries. Thus, we identified a new transport protein at the BBB that might play an important role in the exclusion of xenobiotics from the brain.
Eisenblätter
Tanja
T
Institut für Biochemie, Westfälische Wilhelms-Universität Münster, Wilhelm-Klemm Str. 2, Münster 48149, Germany
Galla
Hans-Joachim
HJ
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001812:Blood-Brain Barrier; D015152:Blotting, Northern; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D003001:Cloning, Molecular; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D015723:Gene Library; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D010802:Phylogeny; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013552:Swine; D014018:Tissue Distribution
D018435:ATP Binding Cassette Transporter, Subfamily B; D016895:Culture Media, Serum-Free; D018076:DNA, Complementary