Document Detail


VEGF-induced ROS generation from NAD(P)H oxidases protects human leukemic cells from apoptosis.
MedLine Citation:
PMID:  20428783     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS) play critical roles in vascular pathophysiology and in hematological malignancies. VEGF is supposed to utilize ROS as messenger intermediates downstream of the VEGF receptor-2. NAD(P)H oxidase (Nox) family is a major source of cellular ROS and is implicated in increased ROS production in tumor cells. We previously demonstrated that B1647 cells, a human leukemic cell line, express Nox2 and Nox4, both at mRNA and protein level. We suggest here that the VEGF-induced increase in ROS can be related to Nox2 and Nox4 activities. Nox-derived ROS are involved in early signaling events such as the autophosphorylation of VEGF receptor-2, and in the modulation of glucose uptake, a cellular activity strictly bound to VEGF-induced leukemic cell proliferation, as shown by experiments with antioxidants and Nox inhibitors and siRNA. Nox-generated ROS are required to sustain B1647 cell viability and proliferation; in fact, antioxidants such as EUK-134 or Nox inhibitors and siRNA direct cells to apoptotic cell death, suggesting that manipulation of cellular Nox2 and Nox4 could affect survival of leukemic cells.
Authors:
Tullia Maraldi; Cecilia Prata; Cristiana Caliceti; Francesco Vieceli Dalla Sega; Laura Zambonin; Diana Fiorentini; Gabriele Hakim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  36     ISSN:  1791-2423     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-04-29     Completed Date:  2010-08-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1581-9     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:
Apoptosis / physiology*
Blotting, Western
Cell Line, Tumor
Electrophoresis, Polyacrylamide Gel
Humans
Immunoprecipitation
Leukemia / metabolism*,  pathology
Membrane Glycoproteins / metabolism*
NADPH Oxidase / metabolism*
RNA Interference
Reactive Oxygen Species / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Vascular Endothelial Growth Factor A / metabolism*
Chemical
Reg. No./Substance:
0/CYBB protein, human; 0/Membrane Glycoproteins; 0/Reactive Oxygen Species; 0/Vascular Endothelial Growth Factor A; EC 1.6.3.-/NOX4 protein, human; EC 1.6.3.1/NADPH Oxidase

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