Document Detail


Copper ability to induce premature senescence in human fibroblasts.
MedLine Citation:
PMID:  21695420     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human diploid fibroblasts (HDFs) exposed to subcytotoxic concentrations of oxidative or stressful agents, such as hydrogen peroxide, tert-butylhydroperoxide, or ethanol, undergo stress-induced premature senescence (SIPS). This condition is characterized by the appearance of replicative senescence biomarkers such as irreversible growth arrest, increase in senescence-associated β-galactosidase (SA β-gal) activity, altered cell morphology, and overexpression of several senescence-associated genes. Copper is an essential trace element known to accumulate with ageing and to be involved in the pathogenesis of some age-related disorders. Past studies using either yeast or human cellular models of ageing provided evidence in favor of the role of intracellular copper as a longevity modulator. In the present study, copper ability to cause the appearance of senescent features in HDFs was assessed. WI-38 fibroblasts exposed to a subcytotoxic concentration of copper sulfate presented inhibition of cell proliferation, cell enlargement, increased SA β-gal activity, and mRNA overexpression of several senescence-associated genes such as p21, apolipoprotein J (ApoJ), fibronectin, transforming growth factor β-1 (TGF β1), insulin growth factor binding protein 3, and heme oxygenase 1. Western blotting results confirmed enhanced intracellular p21, ApoJ, and TGF β1 in copper-treated cells. Thus, similar to other SIPS-inducing agents, HDF exposure to subcytotoxic concentration of copper results in premature senescence. Further studies will unravel molecular mechanisms and the biological meaning of copper-associated senescence and lead to a better understanding of copper-related disorder establishment and progression.
Authors:
Liliana Matos; Alexandra Gouveia; Henrique Almeida
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-06-22
Journal Detail:
Title:  Age (Dordrecht, Netherlands)     Volume:  34     ISSN:  1574-4647     ISO Abbreviation:  Age (Dordr)     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-26     Completed Date:  2012-12-20     Revised Date:  2013-08-19    
Medline Journal Info:
Nlm Unique ID:  101250497     Medline TA:  Age (Dordr)     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  783-94     Citation Subset:  IM    
Affiliation:
Faculty of Nutrition and Food Sciences, University of Porto, Rua Dr. Roberto Frias, Oporto, Portugal. lmatos@fcna.up.pt
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Cell Aging / drug effects*,  physiology
Cell Proliferation / drug effects*
Cells, Cultured / cytology,  drug effects
Clusterin / genetics,  metabolism*
Copper Sulfate / pharmacology*
Fibroblasts / cytology,  drug effects
Humans
Oxidative Stress / drug effects*
RNA, Messenger / metabolism
Real-Time Polymerase Chain Reaction / methods
Reference Values
Sampling Studies
Sensitivity and Specificity
Signal Transduction
beta-Galactosidase / drug effects,  metabolism
Chemical
Reg. No./Substance:
0/Clusterin; 0/RNA, Messenger; 7758-98-7/Copper Sulfate; EC 3.2.1.23/beta-Galactosidase
Comments/Corrections

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