Document Detail


Insulin-like growth factor-1-mediated AKT activation postpones the onset of ultraviolet B-induced apoptosis, providing more time for cyclobutane thymine dimer removal in primary human keratinocytes.
MedLine Citation:
PMID:  12070137     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Insulin-like growth factor-1 (IGF-1) acts as a potent survival factor in numerous cell lines, primarily through activation of the AKT signaling pathway. Although some targets of this pathway have known anti-apoptotic functions, its relationship with the improved survival of cells after exposure to environmental stresses, including UVB, remains largely unclear. We report that in growth factor-deprived keratinocytes, IGF-1 significantly and consistently delayed the onset of UVB-induced apoptosis by >7 h. This delay allowed IGF-1-supplemented keratinocytes to repair significantly more cyclobutane thymine dimers than their growth factor-deprived counterparts. This increase in cyclobutane thymine removal resulted in enhanced survival if the amount of DNA damage was not too high. To increase cell survival after UVB irradiation, IGF-1 supplementation was required only during this initial time period in which extra repair was executed. Finally, we show that IGF-1 mediated this delay in the onset of UVB-induced apoptosis through activation of the AKT signaling pathway. We therefore believe that the AKT signaling pathway increases cell survival after a genotoxic insult such as UVB irradiation not by inhibiting the apoptotic stimulus, but only by postponing the induction of apoptosis, giving the DNA repair mechanism more time to work.
Authors:
David Decraene; Patrizia Agostinis; Roger Bouillon; Hugo Degreef; Marjan Garmyn
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2002-06-17
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  277     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-09-02     Completed Date:  2002-10-29     Revised Date:  2012-06-22    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  32587-95     Citation Subset:  IM    
Affiliation:
Department of Dermatology, Faculty of Medicine, Katholieke Universiteit, B-3000 Leuven, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis*
Blotting, Southern
Blotting, Western
Cell Survival
Cells, Cultured
Coloring Agents / pharmacology
DNA Damage
DNA Repair
Dose-Response Relationship, Drug
Enzyme Activation
Enzyme Inhibitors / pharmacology
Humans
Imidazoles / pharmacology
Insulin-Like Growth Factor I / pharmacology*
Keratinocytes / metabolism*
Phosphatidylinositol 3-Kinases / metabolism
Phosphorylation
Protein-Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins / metabolism*
Proto-Oncogene Proteins c-akt
Pyrimidine Dimers / metabolism*
Signal Transduction
Tetrazolium Salts / pharmacology
Thiazoles / pharmacology
Thymine / metabolism
Time Factors
Ultraviolet Rays*
Chemical
Reg. No./Substance:
0/Coloring Agents; 0/Enzyme Inhibitors; 0/Imidazoles; 0/PD 169316; 0/Proto-Oncogene Proteins; 0/Pyrimidine Dimers; 0/Tetrazolium Salts; 0/Thiazoles; 298-93-1/thiazolyl blue; 65-71-4/Thymine; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.1.-/3-phosphoinositide-dependent protein kinase; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/AKT1 protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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