Signal transduction in H2O2-induced senescence-like phenotype in human diploid fibroblasts

Frippiat, Christophe; Dewelle, Janique; Remacle, José; Toussaint, Olivier

doi:10.1016/s0891-5849(02)01044-4

Cited by 109 publications

(76 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…TGF β1 was shown to be overexpressed in replicative, t-BHP-, and ethanol-induced senescence of WI-38 HDFs ). More specifically, it has already been demonstrated that TGF β1 overexpression is required for the appearance of several biomarkers of cellular senescence, such as the induction of senescent morphogenesis, increased mRNA level of senescence-associated genes, such as ApoJ and fibronectin, and increased senescenceassociated β-galactosidase activity, after exposure of HDFs to subcytotoxic stress with H 2 O 2 (Frippiat et al 2001;Frippiat et al 2002) or UVB . Similar to other stress-induced premature senescence cellular models, WI-38 HDFs exposed to 250 μM copper sulfate was followed by increased mRNA and protein levels of TGF β1.…”

Section: Discussionmentioning

confidence: 99%

Copper ability to induce premature senescence in human fibroblasts

Matos

Gouveia

Almeida

2011

AGE

View full text Add to dashboard Cite

Human diploid fibroblasts (HDFs) exposed to subcytotoxic concentrations of oxidative or stressful agents, such as hydrogen peroxide, tertbutylhydroperoxide, or ethanol, undergo stressinduced 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 senescenceassociated 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 SIPSinducing 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.

show abstract

Section: Discussionmentioning

confidence: 99%

Copper ability to induce premature senescence in human fibroblasts

Matos

Gouveia

Almeida

2011

AGE

View full text Add to dashboard Cite

show abstract

“…Anyway, among the genes with increased mRNA levels in old tissue, TGF-β1 is probably the most interesting: it induces the appearance of biomarkers of senescence in prematurely senescent fibroblasts like the over-expression of SM22. GPX is up-regulated in prematurely senescent human fibroblasts after exposure to sublethal oxidant stress Frippiat et al 2001Frippiat et al , 2002Pascal et al 2005). In this context, the most interesting genes are TGF-β1, SM22 and GPX which are upregulated in replicative senescence, premature senescence and dermis biopsies of aged donors.…”

Section: Discussionmentioning

confidence: 99%

“…TGF-β1 is overexpressed in skin in vivo after UVB exposure (Quan et al 2002b), as well in human skin diploid fibroblasts (HDFs) in replicative senescence or in stress-induced premature senescence induced by UVB, H 2 O 2 , ethanol or tert-butylhydroperoxide (t-BHP) (Debacq- Frippiat et al 2001Frippiat et al , 2002Pascal et al 2005). The fact that the dermis biopsies were from regions of the body not intensely exposed to UVB suggest that TGF-β1 over-expression found herein could be due to intrinsic aging only.…”

Section: Low Density Cdna Microarray Experiments and Data Analysismentioning

confidence: 99%

Expression profiling of senescent-associated genes in human dermis from young and old donors. Proof-of-concept study

et al. 2008

Self Cite

View full text Add to dashboard Cite

It is often described that it is difficult to really discriminate the cause of intrinsic skin aging. The aim of this study was to compare the profiles of expression of senescence-associated genes in biopsies of dermis from young and old human donors. TGF-β1 was up-regulated in the dermis of old donors as well as the TGF-β1 -regulated genes. The anti-oxidant enzymes Selenium-dependent Glutathione peroxidase and Glutatione STransferase Theta 1 were also up-regulated in old dermis as well as Tumor Necrosis Factor Receptor Superfamily 1A. None of these genes had altered expression level in skin fibroblasts embedded in a collagen matrix and exposed to sublethal doses of UVB, suggesting their involvement in intrinsic aging. This study represents a proof-of-concept of larger whole transcriptome studies where all avenues should be used to subtract changes in gene expression due to extrinsic aging from changes potentially due to intrinsic aging.

show abstract

“…Because both TGF-␤ and p38 MAPK have been implicated in controlling oxidative stress-induced FN synthesis, [43][44][45] we tested whether their neutralization affected senescence-associated FN release. These experiments showed that a t-BHP-induced increase in cell-associated FN could be reduced to control levels with a TGF-␤1-blocking antibody ( Figure 5C).…”

Section: Senescence-associated Oxidative Stress As a Cause Of Increasmentioning

confidence: 99%

“…44,54 Interestingly, it has been reported that TGF-␤1 could also phosphorylate p38 MAPK 45 and that neutralization of TGF-␤1 reduced the enhanced activity of p38 MAPK in cells under oxidative stress. 44 We observed similar effects in HOMCs, which indicated that, on the one hand, TGF-␤1 could be induced by a p38 MAPK-dependent mechanism, and on the other hand, it could activate p38 MAPK. Furthermore, we showed that p38 MAPK mediated TGF-␤1-induced FN synthesis.…”

Section: Senescent Mcs and Ovarian Cancer 1237mentioning

confidence: 99%

Senescent Peritoneal Mesothelial Cells Promote Ovarian Cancer Cell Adhesion

Książek

Mikuła-Pietrasik

Korybalska

et al. 2009

The American Journal of Pathology

View full text Add to dashboard Cite

Adhesion of ovarian cancer cells to the peritoneal mesothelium is a key step in the malignant progression of the disease. In an in vitro study, we showed that the adherence of ovarian cancer cells (of the OVCAR-3, SKOV-3, and A2780 cell lines) to senescent human omentum-derived peritoneal mesothelial cells (HOMCs) was greater than to early passage cells. The process was mediated primarily by the increased interaction of the ␣5␤1 integrin on cancer cells with HOMC-associated fibronectin (FN). In comparison with early passage HOMCs, senescent cells exhibited increased FN mRNA expression levels and produced significantly more FN. To assess the effect of senescence-associated oxidative stress on FN release, HOMCs were rendered senescent by exposure to an oxidant, tert-butyl hydroperoxide. Treatment with tert-butyl hydroperoxide resulted in a significant increase in HOMC FN mRNA and protein expression levels. The effect of oxidative stress on FN synthesis was found to be mediated by transforming growth factor-␤1, whose signaling pathway was controlled at upstream and downstream levels by p38 MAPK. The activity of p38 MAPK increased markedly in senescent HOMCs. Treatment of HOMCs with antioxidants significantly attenuated senescence-associated increases in p38 MAPK activity, production of both transforming growth factor-␤1 and FN, and ovarian cancer cell adhesion. These data indicate that oxidative stress that accompanies senescence may increase Ovarian cancer is still associated with high mortality. The poor outcome is related to a large extent to metastatic spreading of cancer cells within the peritoneal cavity. Attachment of malignant cells to the peritoneal mesothelium is thought to be a critical step in peritoneal dissemination of the disease. Available data indicate that the process is mediated by interactions between extracellular matrix components produced by mesothelial cells and the corresponding adhesion molecules on ovarian cancer cells. A key role is thought to be played by CD44 and ␤1 integrin receptors and their ligands-hyaluronan, fibronectin (FN), and vitronectin. [2][3][4][5][6] FN is a ubiquitous constituent of extracellular matrix. Secreted by cells as a soluble dimer, it is then processed and assembled into insoluble fibrils at the cell surface. 7 FN is involved in many cellular functions including the maintenance of cell shape, tissue repair, cell differentiation, adhesion, and migration. These processes are primarily mediated by binding of the Arg-Gly-Asp (RGD) sequence of the FN molecule to integrin receptors (especially to ␣5␤1 and ␣ V ␤3).8 It has been demonstrated that FN released by peritoneal mesothelial cells stimulates ovarian cancer cell motility in vitro.9 Moreover, competitive inhibition of FN by RGD-containing peptides has been reported to decrease peritoneal spreading of ovarian cancer cells in mice. 10 More recently it has been demonstrated that the attachment of ovarian cancer cells to the peritoneum results in up-regulation of their matrix metalloproteinase-2, which cleaves mesot...

show abstract

Signal transduction in H2O2-induced senescence-like phenotype in human diploid fibroblasts

Cited by 109 publications

References 34 publications

Copper ability to induce premature senescence in human fibroblasts

Copper ability to induce premature senescence in human fibroblasts

Expression profiling of senescent-associated genes in human dermis from young and old donors. Proof-of-concept study

Senescent Peritoneal Mesothelial Cells Promote Ovarian Cancer Cell Adhesion

Contact Info

Product

Resources

About