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NAMPT is essential for the G-CSF–induced myeloid differentiation via a NAD+–sirtuin-1–dependent pathway.
- Source :
-
Nature Medicine . Feb2009, Vol. 15 Issue 2, p151-158. 8p. 6 Graphs. - Publication Year :
- 2009
-
Abstract
- We identified nicotinamide phosphoribosyltransferase (NAMPT), also known as pre-B cell colony enhancing factor (PBEF), as an essential enzyme mediating granulocyte colony-stimulating factor (G-CSF)-triggered granulopoiesis in healthy individuals and in individuals with severe congenital neutropenia. Intracellular NAMPT and NAD+ amounts in myeloid cells, as well as plasma NAMPT and NAD+ levels, were increased by G-CSF treatment of both healthy volunteers and individuals with congenital neutropenia. NAMPT administered both extracellularly and intracellularly induced granulocytic differentiation of CD34+ hematopoietic progenitor cells and of the promyelocytic leukemia cell line HL-60. Treatment of healthy individuals with high doses of vitamin B3 (nicotinamide), a substrate of NAMPT, induced neutrophilic granulocyte differentiation. The molecular events triggered by NAMPT include NAD+-dependent sirtuin-1 activation, subsequent induction of CCAAT/enhancer binding protein-α and CCAAT/enhancer binding protein-β, and, ultimately, upregulation of G-CSF synthesis and G-CSF receptor expression. G-CSF, in turn, further increases NAMPT levels. These results reveal a decisive role of the NAD+ metabolic pathway in G-CSF-triggered myelopoiesis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10788956
- Volume :
- 15
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Nature Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 36386725
- Full Text :
- https://doi.org/10.1038/nm.1913