Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/101034
Author(s): Liliana Matos
Alexandra Gouveia
Henrique Almeida
Title: Copper ability to induce premature senescence in human fibroblasts
Issue Date: 2012
Abstract: 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.
Description: 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.
Subject: Ciências da Saúde, Medicina clínica
Health sciences, Clinical medicine
Scientific areas: Ciências médicas e da saúde::Medicina clínica
Medical and Health sciences::Clinical medicine
URI: https://repositorio-aberto.up.pt/handle/10216/101034
Document Type: Artigo em Revista Científica Internacional
Rights: restrictedAccess
Appears in Collections:FCNAUP - Artigo em Revista Científica Internacional
FMUP - Artigo em Revista Científica Internacional

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