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rdf:type |
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lifeskim:mentions |
umls-concept:C0010556,
umls-concept:C0015252,
umls-concept:C0018270,
umls-concept:C0022567,
umls-concept:C0040092,
umls-concept:C0040223,
umls-concept:C0086418,
umls-concept:C0162638,
umls-concept:C0164786,
umls-concept:C0205225,
umls-concept:C0332162,
umls-concept:C0728940,
umls-concept:C0812228,
umls-concept:C1879547
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pubmed:issue |
36
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pubmed:dateCreated |
2002-9-2
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-phosphoinositide-dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Coloring Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/PD 169316,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidine Dimers,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrazolium Salts,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Thymine,
http://linkedlifedata.com/resource/pubmed/chemical/thiazolyl blue
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
32587-95
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12070137-Apoptosis,
pubmed-meshheading:12070137-Blotting, Southern,
pubmed-meshheading:12070137-Blotting, Western,
pubmed-meshheading:12070137-Cell Survival,
pubmed-meshheading:12070137-Cells, Cultured,
pubmed-meshheading:12070137-Coloring Agents,
pubmed-meshheading:12070137-DNA Damage,
pubmed-meshheading:12070137-DNA Repair,
pubmed-meshheading:12070137-Dose-Response Relationship, Drug,
pubmed-meshheading:12070137-Enzyme Activation,
pubmed-meshheading:12070137-Enzyme Inhibitors,
pubmed-meshheading:12070137-Humans,
pubmed-meshheading:12070137-Imidazoles,
pubmed-meshheading:12070137-Insulin-Like Growth Factor I,
pubmed-meshheading:12070137-Keratinocytes,
pubmed-meshheading:12070137-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12070137-Phosphorylation,
pubmed-meshheading:12070137-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12070137-Proto-Oncogene Proteins,
pubmed-meshheading:12070137-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:12070137-Pyrimidine Dimers,
pubmed-meshheading:12070137-Signal Transduction,
pubmed-meshheading:12070137-Tetrazolium Salts,
pubmed-meshheading:12070137-Thiazoles,
pubmed-meshheading:12070137-Thymine,
pubmed-meshheading:12070137-Time Factors,
pubmed-meshheading:12070137-Ultraviolet Rays
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pubmed:year |
2002
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pubmed:articleTitle |
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.
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pubmed:affiliation |
Department of Dermatology, Faculty of Medicine, Katholieke Universiteit, B-3000 Leuven, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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