title: Identification of CXCR4 as a new nitric oxide-regulated gene in human CD34+ cells.
abstract: As an intracellular second messenger, nitric oxide (NO) is increasingly implicated in the control of transcriptional machinery and gene expression. Here, we show that cell surface expression of CXCR4 on CD34(+) cells was increased in a dose- and time-dependent manner in response to NO donors. Augmented surface expression was correlated with an increase in CXCR4 mRNA level. A specific NO scavenger prevented the elevation in CXCR4 mRNA caused by NO donors, suggesting a direct signaling action mediated by NO on CXCR4 transcription. NO treatment had no significant effect on CXCR4 mRNA stability. However, induction of CXCR4 mRNA by NO was still observed in conditions in which initiation of translation was inhibited, suggesting that the NO effect must be mediated by a pre-existing protein. CXCR4 mRNA induction did not involve cGMP (guanosine 3', 5'-cyclic monophosphate) generation but was most likely mediated via oxidation of intracellular protein thiols. Finally, CD34(+) cells pretreated with NO donors exhibited an increased chemotactic response. This study demonstrates that the NO pathway can modulate CXCR4 expression in human CD34(+) cells and suggests that NO may play a critical role in the trafficking of hematopoietic progenitors.
authors.affiliation: INSERM U790, Institut Gustave Roussy, PR1, Villejuif, France.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Monika
authors.initials: M
authors.lastname: Wittner
authors.forename: Hakim
authors.initials: H
authors.lastname: Bouamar
authors.forename: Peggy
authors.initials: P
authors.lastname: Jarrier
authors.forename: William
authors.initials: W
authors.lastname: Vainchenker
authors.forename: Fawzia
authors.initials: F
authors.lastname: Louache
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D007700:Kinetics; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D018952:Antigens, CD34; D017931:DNA Primers; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D012333:RNA, Messenger; D019718:Receptors, CXCR4; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide