Expression and induction of p-glycoprotein-1 on cultured human brain endothelium.
The ABC-transporter, p-glycoprotein-1 (pgp-1), is expressed on brain endothelium and is reported to be induced by several cytotoxic drugs, which are themselves substrates of pgp-1. Pgp-1 was increased on a human brain endothelial cell line (hCMEC/D3) after treatment with puromycin or verapamil. However, flow cytometry showed that the apparent upregulation caused by puromycin was not because of a global increase in expression levels, but selective cell death of a subpopulation of endothelium expressing the lowest levels of pgp-1. If a cytotoxic substrate of pgp-1 increases pgp-1 expression in vitro, it can easily be misinterpreted as a transcriptional activator of pgp-1.
Male
David K
DK
Department of Life Sciences, The Open University, Milton Keynes, UK. D.K.Male@Open.ac.uk
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis*; D001921:Brain / Q000098:blood supply*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects; D011691:Puromycin / Q000494:pharmacology; D013379:Substrate Specificity; D015533:Transcriptional Activation / Q000187:drug effects; D014466:Ultraviolet Rays; D014700:Verapamil / Q000494:pharmacology; D000097202:ATP-Binding Cassette Sub-Family B Member 4
D018435:ATP Binding Cassette Transporter, Subfamily B; D011691:Puromycin; D014700:Verapamil; D000097202:ATP-Binding Cassette Sub-Family B Member 4