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    
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.
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    
Department of Dermatology, Faculty of Medicine, Katholieke Universiteit, B-3000 Leuven, Belgium.
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MeSH Terms
Blotting, Southern
Blotting, Western
Cell Survival
Cells, Cultured
Coloring Agents / pharmacology
DNA Damage
DNA Repair
Dose-Response Relationship, Drug
Enzyme Activation
Enzyme Inhibitors / pharmacology
Imidazoles / pharmacology
Insulin-Like Growth Factor I / pharmacology*
Keratinocytes / metabolism*
Phosphatidylinositol 3-Kinases / metabolism
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*
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 protein, human; EC Kinases; EC Proteins c-akt

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

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