Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetophenones / pharmacology
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Antigens, CD34 / analysis
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Blotting, Western
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Bone Marrow Cells / cytology
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / metabolism*
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Catalase / genetics
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Catalase / metabolism
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Chromones / pharmacology
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Enzyme Inhibitors / pharmacology
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Flow Cytometry
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Gene Expression Regulation, Enzymologic / drug effects
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Glutathione Peroxidase / genetics
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Glutathione Peroxidase / metabolism
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Glutathione Peroxidase GPX1
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / metabolism*
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Humans
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Hydrogen Peroxide / metabolism
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Immunohistochemistry
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Microscopy, Confocal
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Models, Biological
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Morpholines / pharmacology
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NADPH Oxidases / genetics*
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NADPH Oxidases / metabolism
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Onium Compounds / pharmacology
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Reactive Oxygen Species / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Superoxide Dismutase / genetics
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Superoxide Dismutase / metabolism
Substances
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Acetophenones
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Antigens, CD34
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Chromones
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Enzyme Inhibitors
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Isoenzymes
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Morpholines
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Onium Compounds
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Reactive Oxygen Species
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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diphenyleneiodonium
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acetovanillone
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Hydrogen Peroxide
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Catalase
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Glutathione Peroxidase
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Superoxide Dismutase
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NADPH Oxidases
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Glutathione Peroxidase GPX1
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GPX1 protein, human