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The Stem Cell Marker Bcrp/ABCG2 Enhances Hypoxic Cell Survival through Interactions with Heme
Ist Teil von
The Journal of biological chemistry, 2004-06, Vol.279 (23), p.24218-24225
Ort / Verlag
United States: American Society for Biochemistry and Molecular Biology
Erscheinungsjahr
2004
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Our studies demonstrate that the ABC transporter and marker of stem and progenitor cells known as the breast cancer resistance
protein (BCRP or ABCG2) confers a strong survival advantage under hypoxic conditions. We show that, under hypoxia, progenitor
cells from Bcrp â / â mice have a reduced ability to form colonies as compared with progenitor cells from Bcrp +/+ mice. Blocking BCRP function in Bcrp +/+ progenitor cells markedly reduces survival under hypoxic conditions. However, blocking heme biosynthesis reverses the hypoxic
susceptibility of Bcrp â/â progenitor cells, a finding that indicates that heme molecules ( i.e. porphyrins) are detrimental to Bcrp â/â cells under hypoxia. BCRP specifically binds heme, and cells lacking BCRP accumulate porphyrins. Finally, Bcrp expression is up-regulated by hypoxia, and we demonstrate that this up-regulation involves the hypoxia-inducible transcription
factor complex HIF-1. Collectively, our findings suggest that cells can, upon hypoxic demand, use BCRP to reduce heme or porphyrin
accumulation, which can be detrimental to cells. Our findings have implications for the survival of stem cells and tumor cells
in hypoxic environments.