Subcytotoxic H2O2 Stress Triggers a Release of Transforming Growth Factor-β1, Which Induces Biomarkers of Cellular Senescence of Human Diploid Fibroblasts

Christophe Frippiat, Qin Chen, Stephanie Zdanov, Joao Padro Magalhaes, Jose Remacle, Olivier Toussaint

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Abstract

Stress-induced premature senescence (SIPS) is induced 3 days after exposure of human diploid fibroblasts to subcytotoxic oxidative stress with H2O2, with appearance of several biomarkers of replicative senescence. In this work, we show that transforming growth factor-β1 (TGF-β1) regulates the induction of several of these biomarkers in SIPS: cellular morphology, senescence-associated β-galactosidase activity, increase in the steady-state level of fibronectin, apolipoprotein J, osteonectin, and SM22 mRNA. Indeed, the neutralization of TGF-β1 or its receptor (TGF-β RII) using specific antibodies decreases sharply the percentage of cells positive for the senescent-associated β-galactosidase activity and displaying a senescent morphology. In the presence of each of these antibodies, the steady-state level of fibronectin, osteonectin, apolipoprotein J, and SM22 mRNA is no more increased at 72 h after stress. Results obtained on fibroblasts retrovirally transfected with the human papillomavirus E7 cDNA suggest that retinoblastoma protein (Rb) regulates the expression of TGF-β1 in stressful conditions, leading to SIPS and overexpression of these four genes.

Original languageEnglish (US)
Pages (from-to)2531-2537
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number4
DOIs
StatePublished - Jan 26 2001

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Cell Aging
Transforming Growth Factors
Biomarkers
Fibroblasts
Diploidy
Osteonectin
Galactosidases
Clusterin
Fibronectins
Retinoblastoma Protein
Messenger RNA
Antibodies
Oxidative stress
Oxidative Stress
Complementary DNA
Genes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Subcytotoxic H2O2 Stress Triggers a Release of Transforming Growth Factor-β1, Which Induces Biomarkers of Cellular Senescence of Human Diploid Fibroblasts. / Frippiat, Christophe; Chen, Qin; Zdanov, Stephanie; Magalhaes, Joao Padro; Remacle, Jose; Toussaint, Olivier.

In: Journal of Biological Chemistry, Vol. 276, No. 4, 26.01.2001, p. 2531-2537.

Research output: Contribution to journalArticle

Frippiat, Christophe ; Chen, Qin ; Zdanov, Stephanie ; Magalhaes, Joao Padro ; Remacle, Jose ; Toussaint, Olivier. / Subcytotoxic H2O2 Stress Triggers a Release of Transforming Growth Factor-β1, Which Induces Biomarkers of Cellular Senescence of Human Diploid Fibroblasts. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 4. pp. 2531-2537.
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