| Repeated exposures to UVB induce differentiation rather than senescence of human keratinocytes lacking p16(INK-4A). | |
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MedLine Citation:
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PMID: 19554468 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Skin cancers and extrinsic aging are delayed consequences of cumulative UV radiation insults. Exposure of human keratinocytes to UVB has been previously shown to trigger premature senescence. In order to explore the involvement of the cyclin-dependent kinase inhibitor p16(INK-4a) in UVB-induced premature senescence, we developed an original model of repeated sublethal exposures of human keratinocytes deficient in p16(INK-4a). We did not observe any significant increase of senescence-associated beta-galactosidase activity positive cells following UVB exposure in this cell line in contrast to primary keratinocytes, suggesting a role for p16(INK-4a) in UVB-induced senescence. However, we detected sustained DNA damage, prolonged cell cycle arrest, and induction of markers of epidermal differentiation like involucrin and filaggrin as consequences of the repeated exposures. Keratinocytes exposed to the same dose of UVB in a single exposure died. Furthermore, the abundance of the keratins 6, 16 and 17 was increased in keratinocytes exposed repeatedly to UVB suggesting an alternative differentiation. This model allows the induction of a state of differentiation observed in vivo with differentiation uncoupled from premature senescence. |
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Authors:
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V?ronique Bertrand-Vallery; Emmanuelle Boilan; No?lle Ninane; Catherine Demazy; Bertrand Friguet; Olivier Toussaint; Yves Poumay; Florence Debacq-Chainiaux |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-06-24 |
Journal Detail:
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Title: Biogerontology Volume: 11 ISSN: 1389-5729 ISO Abbreviation: Biogerontology Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-03 Completed Date: 2010-05-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100930043 Medline TA: Biogerontology Country: Netherlands |
Other Details:
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Languages: eng Pagination: 167-81 Citation Subset: IM |
Affiliation:
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Research Unit of Cellular Biology, Department of Biology, University of Namur, Rue de Bruxelles 61, Namur, Belgium. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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radiation effects Cell Aging / radiation effects* Cell Cycle / radiation effects Cell Differentiation / radiation effects* Cells, Cultured Cyclin-Dependent Kinase Inhibitor p16 / metabolism* Cyclin-Dependent Kinase Inhibitor p21 / metabolism DNA Damage / radiation effects Dose-Response Relationship, Radiation Humans Intermediate Filament Proteins / metabolism Keratinocytes / cytology, metabolism*, radiation effects* Keratins / metabolism Protein Precursors / metabolism Tumor Suppressor Protein p53 / metabolism Ultraviolet Rays* beta-Galactosidase / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cyclin-Dependent Kinase Inhibitor p16; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Intermediate Filament Proteins; 0/Protein Precursors; 0/Tumor Suppressor Protein p53; 0/filaggrin; 60108-77-2/involucrin; 68238-35-7/Keratins; EC 3.2.1.23/beta-Galactosidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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