| p53-dependent ICAM-1 overexpression in senescent human cells identified in atherosclerotic lesions. | |
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MedLine Citation:
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PMID: 15711569 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Most normal somatic cells enter a state called replicative senescence after a certain number of divisions, characterized by irreversible growth arrest. Moreover, they express a pronounced inflammatory phenotype that could contribute to the aging process and the development of age-related pathologies. Among the molecules involved in the inflammatory response that are overexpressed in senescent cells and aged tissues is intercellular adhesion molecule-1 (ICAM-1). Furthermore, ICAM-1 is overexpressed in atherosclerosis, an age-related, chronic inflammatory disease. We have recently reported that the transcriptional activator p53 can trigger ICAM-1 expression in an nuclear factor-kappa B (NF-kappaB)-independent manner (Gorgoulis et al, EMBO J. 2003; 22: 1567-1578). As p53 exhibits an increased transcriptional activity in senescent cells, we investigated whether p53 activation is responsible for the senescence-associated ICAM-1 overexpression. To this end, we used two model systems of cellular senescence: (a) human fibroblasts and (b) conditionally immortalized human vascular smooth muscle cells. Here, we present evidence from both cell systems to support a p53-mediated ICAM-1 overexpression in senescent cells that is independent of NF-kappaB. We also demonstrate in atherosclerotic lesions the presence of cells coexpressing activated p53, ICAM-1, and stained with the senescence-associated beta-galactosidase, a biomarker of replicative senescence. Collectively, our data suggest a direct functional link between p53 and ICAM-1 in senescence and age-related disorders. |
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Authors:
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Vassilis G Gorgoulis; Harris Pratsinis; Panayotis Zacharatos; Catherine Demoliou; Fragiska Sigala; Panayiotis J Asimacopoulos; Athanasios G Papavassiliou; Dimitris Kletsas |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Laboratory investigation; a journal of technical methods and pathology Volume: 85 ISSN: 0023-6837 ISO Abbreviation: Lab. Invest. Publication Date: 2005 Apr |
Date Detail:
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Created Date: 2005-03-21 Completed Date: 2005-05-26 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376617 Medline TA: Lab Invest Country: United States |
Other Details:
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Languages: eng Pagination: 502-11 Citation Subset: IM |
Affiliation:
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Department of Histology and Embryology, Medical School, University of Athens, Athens, Greece. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Arteriosclerosis
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metabolism* Base Sequence Cell Aging DNA Primers Humans Immunohistochemistry Intercellular Adhesion Molecule-1 / metabolism* NF-kappa B / metabolism RNA, Messenger / genetics Tumor Suppressor Protein p53 / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/NF-kappa B; 0/RNA, Messenger; 0/Tumor Suppressor Protein p53; 126547-89-5/Intercellular Adhesion Molecule-1 |
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