Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells.
Hematopoietic stem cells show reduced staining with a mitochondrial fluorescent dye, rhodamine 123 (Rh-123), which was supposed to indicate decreased mitochondrial activity in these cells. Rh123 and several other fluorescent dyes are substrates for transport mediated by P-glycoprotein (P-gp), an efflux pump responsible for multidrug resistance in tumor cells. We have found that staining of human bone marrow cells with fluorescent dyes is potentiated by P-gp inhibitors and inversely correlated with P-gp expression. P-gp is expressed in practically all hematopoietic progenitor cells, including long-term culture-initiating cells. The highest levels of P-gp among the progenitors are associated with cells displaying characteristics of pluripotent stem cells. These results have implications for stem cell purification and bone marrow resistance to cancer chemotherapy.
Chaudhary
P M
PM
Department of Genetics, University of Illinois, Chicago 60612.
Roninson
I B
IB
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001853:Bone Marrow / Q000378:metabolism; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004351:Drug Resistance / Q000502:physiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005456:Fluorescent Dyes; D008562:Membrane Glycoproteins; D012313:RNA