Bone-marrow derived hematopoietic stem/progenitor cells express multiple isoforms of NADPH oxidase and produce constitutively reactive oxygen species.
Consolidated evidence highlights the importance of redox signalling in poising the balance between self-renewal and differentiation in adult stem cells. The present study shows that human hematopoietic stem/progenitor cells (HSCs) constitutively generate low levels of hydrogen peroxide whose production is inhibited by DPI, apocynin, catalase, and LY294002 and scarcely stimulated by PMA. Moreover, it is shown that HSCs express at the mRNA and protein levels the catalytic subunits of NOX1, NOX2, and NOX4 isoforms of the NADPH oxidase family along with the complete battery of the regulatory subunits p22, p40, p47, p67, rac1, rac2, NOXO1, and NOXA1 as well as the splicing variant NOX2s and that the three NOX isoforms are largely co-expressed in the same HSC. These findings are interpreted in terms of a positive feed-back mechanism of NOXs activation enabling a fine tuning of the ROS level to be possibly used in redox-mediated signalling for growth and differentiation of HSCs.
Piccoli
Claudia
C
Department of Biomedical Science, University of Foggia, viale L. Pinto OO.RR., 71100 Foggia, Italy.
D'Aprile
Annamaria
A
Ripoli
Maria
M
Scrima
Rosella
R
Lecce
Lucia
L
Boffoli
Domenico
D
Tabilio
Antonio
A
Capitanio
Nazzareno
N
D000098:Acetophenones / Q000494:pharmacology; D018952:Antigens, CD34 / Q000032:analysis; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
D000098:Acetophenones; D018952:Antigens, CD34; D002867:Chromones; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009025:Morpholines; D009861:Onium Compounds; D017382:Reactive Oxygen Species; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C007517:diphenyleneiodonium; C056165:acetovanillone; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human