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.