Copper ability to induce premature senescence in human fibroblasts

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Liliana Matos (Author) FCNAUP; Alexandra Gouveia (Author) FCNAUP; Henrique Almeida (Author) FMUP

Journal

Title: Age

Vol. 34

Pages: 783-794

ISSN: 0161-9152

Publisher: Kluwer Academic Publishers

Indexing

ISI Web of Knowledge - 40 Citations

ISI Web of Science

Scopus - 39 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

CORDIS: Health sciences

Other information

Authenticus ID: P-002-7FE

DOI: 10.1007/s11357-011-9276-7

Resumo (PT): 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 -galactosidase (SA -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 favour 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 -gal activity, and mRNA overexpression of several senescence-associated genes such as p21, apolipoprotein J (ApoJ), Fibronectin, Transforming growth factor -1 (TGF 1), Insulin growth factor binding protein 3 (IGFBP3) and Heme oxygenase 1 (HO-1). Western blotting results confirmed enhanced intracellular p21, ApoJ and TGF 1 in copper treated cells. Thus, similarly to other SIPS inducing agents, HDFs 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 disorders establishment and progression.

Abstract (EN): 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 beta-galactosidase (SA beta-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 beta-gal activity, and mRNA overexpression of several senescence-associated genes such as p21, apolipoprotein J (ApoJ), fibronectin, transforming growth factor beta-1 (TGF beta 1), insulin growth factor binding protein 3, and heme oxygenase 1. Western blotting results confirmed enhanced intracellular p21, ApoJ, and TGF beta 1 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12