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First published online October 5, 2006
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2006-0468v1
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Submitted on July 26, 2006
Accepted on September 22, 2006

The Stem Cell Niche

Identification of CXCR4 as a New Nitric Oxide Regulated Gene in Human CD34+ Cells

Yanyan Zhang 1, Monika Wittner 1, Hakim Bouamar 1, Peggy Jarrier 1, William Vainchenker 1, Fawzia Louache 1*

1 INSERM U790, Institut Gustave Roussy, PR1, Villejuif, France

* To whom correspondence should be addressed. E-mail: fawl{at}igr.fr.


   Abstract

As an intracellular second messenger, nitric oxide (NO) is increasingly implicated in the control of the 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 increased 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 where initiation of translation was inhibited suggesting that the NO effect must be mediated by a pre-existing protein. CXCR4 mRNA induction did not involve guanosine 3', 5'-cyclic monophosphate (cGMP) generation, but was most likely mediated via oxidation of intracellular protein thiols. Finally, CD34+ cells pre-treated 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.

Key Words. nitric oxide, CXCR4, SDF-1, gene expression, CD34+ cells




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