Zidovudine-induced blockade of the expression and function of the erythropoietin receptor.
Treatment of bone marrow progenitor cells (BMPC) with zidovudine (AZT) at various concentrations (0.5 to 20 microM) in vitro for 24 hr caused a concentration-dependent decrease in erythropoietin (Epo) receptor expression. The decrease in Epo receptors correlated with a decline in mRNA levels of the receptor. These results suggest that AZT-induced down-regulation of Epo receptor expression followed by loss of Epo-receptor mediated signal transduction is a significant contributory factor to AZT-induced erythroid toxicity.
Gogu
S R
SR
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
Malter
J S
JS
Agrawal
K C
KC
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D016049:Didanosine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology*
D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D015215:Zidovudine; D016049:Didanosine