Document Detail


NAD(P)H oxidase isoform Nox2 plays a prosurvival role in human leukaemia cells.
MedLine Citation:
PMID:  19707918     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mechanism involved in the prosurvival effect of interleukin-3 on the human acute myeloid leukaemia cell line M07e is investigated. A decrease in intracellular reactive oxygen species (ROS) content, glucose transport activity and cell survival was observed in the presence of inhibitors of plasma membrane ROS sources, such as diphenylene iodonium and apocynin, and by small interference RNA for Nox2. Moreover, IL-3 incubation stimulated the synthesis of Nox2 cytosolic sub-unit p47phox and glucose transporter Glut1. Thus, the inhibition of ROS generation by Nox inhibitors stimulated apoptosis showing that ROS production, induced by IL-3 via Nox2, protects leukaemic cells from cell death. Also incubation with receptor tyrosine kinase inhibitors, such as anti-leukaemic drugs blocking the stem cell factor receptor (c-kit), showed similar effects, hinting that IL-3 transmodulates c-kit phosphorylation. These mechanisms may play an important role in acute myeloid leukaemia treatment, representing a novel therapeutic target.
Authors:
Tullia Maraldi; Cecilia Prata; Francesco Vieceli Dalla Sega; Cristiana Caliceti; Laura Zambonin; Diana Fiorentini; Gabriele Hakim
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Free radical research     Volume:  43     ISSN:  1029-2470     ISO Abbreviation:  Free Radic. Res.     Publication Date:  2009  
Date Detail:
Created Date:  2010-06-17     Completed Date:  2010-10-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  1111-21     Citation Subset:  IM    
Affiliation:
Department of Anatomy and Histology, University of Modena and Reggio Emilia, Modena, Italy.
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MeSH Terms
Descriptor/Qualifier:
Biological Transport
Cell Line, Tumor
Cell Survival / physiology
Glucose Transporter Type 1 / metabolism
Humans
Interleukin-3 / metabolism
Leukemia, Myeloid, Acute / enzymology*,  pathology
Membrane Glycoproteins / metabolism*
NADPH Oxidase / metabolism*
Phosphorylation / drug effects
Reactive Oxygen Species / metabolism
Chemical
Reg. No./Substance:
0/CYBB protein, human; 0/Glucose Transporter Type 1; 0/Interleukin-3; 0/Membrane Glycoproteins; 0/Reactive Oxygen Species; EC 1.6.3.1/NADPH Oxidase

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