Document Detail


4-hydroxynonenal and regulation of cell cycle: effects on the pRb/E2F pathway.
MedLine Citation:
PMID:  15288118     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The hypothesis that 4-hydroxynonenal (HNE), a product of lipid peroxidation, might negatively affect cell proliferation, arose from the observation that lipid peroxidation is very low in tumors. In leukemic cells HNE inhibited cell growth and reduced c-myc and c-myb expression. HNE also induced differentiation in different leukemic cell lines. In HL-60 human leukemic cells, HNE induced the accumulation of cells in the G(0)/G(1) phase of the cell cycle accompanied by a decrease of cyclins D1, D2, and A. Moreover, HNE caused an increase in p21 expression. As cyclin D/CDK2 and cyclin A/CDK2 phosphorylate pRB, these findings suggested that pRb phosphorylation could be affected by HNE. Hypophosphorylated pRb binds and inactivates the E2F transcription factors. HNE induced the dephosphorylation of pRb and the increase in pRb/E2F1 complexes, whereas pRb/E2F4 complexes were reduced, because HNE downregulated E2F4 protein expression. The analysis of E2F binding to the P2 c-myc promoter revealed that HNE caused a decrease in "free" E2F, as well as an increase in pRb (and pRB family members) bound to E2F, with consequent repression of the transcription. In conclusion, HNE reduces E2F transcriptional activity by modifying a number of genes involved in regulation of the pRb/E2F pathway.
Authors:
Giuseppina Barrera; Stefania Pizzimenti; Mario U Dianzani
Related Documents :
7626688 - Threshold expression of cyclin e but not d type cyclins characterizes normal and tumour...
18284548 - The antiproliferative activity of melatonin in b65 rat dopaminergic neuroblastoma cells...
17283068 - Involvement of dihydroceramide desaturase in cell cycle progression in human neuroblast...
8832398 - Paradoxical accumulation of the cyclin-dependent kinase inhibitor p27kip1 during the ca...
24120498 - Cd34-negative mesenchymal stem-like cells may act as the cellular origin of human aorti...
23833638 - Induction of erythropoietin increases the cell proliferation rate in a hypoxia-inducibl...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Free radical biology & medicine     Volume:  37     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-03     Completed Date:  2005-02-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  597-606     Citation Subset:  IM    
Affiliation:
Department of Experimental Medicine and Oncology, Section of General Pathology, University of Turin, 10125 Torino, Italy.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Aldehydes / pharmacology*
Cell Cycle / drug effects*
Cyclins / drug effects,  physiology
Growth Inhibitors / pharmacology*
HL-60 Cells
Humans
K562 Cells
Retinoblastoma Protein / drug effects,  metabolism
Transcription, Genetic / drug effects
Chemical
Reg. No./Substance:
0/Aldehydes; 0/Cyclins; 0/Growth Inhibitors; 0/Retinoblastoma Protein; 29343-52-0/4-hydroxy-2-nonenal

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Oxidative stress and apoptosis in metal ion-induced carcinogenesis.
Next Document:  Regulation of 4-hydroxynonenal-mediated signaling by glutathione S-transferases.