Abstract |
Normal human fibroblasts have a limited replicative potential in culture and eventually reach a state of irreversible growth arrest, termed senescence. In a previous study aiming to identify genes that are differentially regulated during cellular senescence we have cloned clusterin/ apolipoprotein J (Apo J), a 80 kDa secreted glycoprotein. In the current report we pursue our studies and show that senescence of human diploid fibroblasts is accompanied by up-regulation of both Apo J mRNA and protein levels, but with no altered biogenesis, binding partner profile or intracellular distribution of the two Apo J forms detected. To analyze the causal relationship between senescence and Apo J protein accumulation, we stably overexpressed the Apo J gene in primary as well as in SV40 T antigen-immortalized human fibroblasts and we showed no alteration of the proliferative capacity of the transduced cells. Despite previous reports on tumor-derived cell lines, overexpression of Apo J in human fibroblasts did not provide protection against apoptosis or growth arrest induced by hydrogen peroxide. Overall, our results suggest that Apo J overexpression does not induce senescence but it is rather a secondary consequence of the senescence phenotype. To our knowledge this is the first report that provides a functional analysis of human Apo J during replicative senescence.
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Authors | C Petropoulou, I P Trougakos, E Kolettas, O Toussaint, E S Gonos |
Journal | FEBS letters
(FEBS Lett)
Vol. 509
Issue 2
Pg. 287-97
(Dec 07 2001)
ISSN: 0014-5793 [Print] England |
PMID | 11741605
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Differentiation
- CLU protein, human
- Clusterin
- Glycoproteins
- Molecular Chaperones
- Recombinant Proteins
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Topics |
- Antigens, Differentiation
(biosynthesis, genetics, isolation & purification)
- Cellular Senescence
(physiology)
- Clusterin
- Diploidy
- Fibroblasts
(cytology, physiology)
- Glycoproteins
(biosynthesis, genetics, isolation & purification)
- Humans
- Molecular Chaperones
(biosynthesis, genetics, isolation & purification)
- Oxidative Stress
(physiology)
- Recombinant Proteins
(biosynthesis)
- Up-Regulation
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