Document Detail


Low-dose UV-radiation sensitizes keratinocytes to TRAIL-induced apoptosis.
MedLine Citation:
PMID:  15137068     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The impact of low-dose ultraviolet light (UV-light) on apoptotic susceptibility of keratinocytes (KCs) induced by TRAIL is unclear. Skin expresses a functional form of TRAIL, and while sun exposure influences TRAIL death receptors, a role for decoy receptors has not been evaluated. Unraveling mechanisms involving apoptotic sensitivity of KCs is important because skin is the first target of UV-light, and a site for commonly occurring cancers. Since apoptosis is a homeostatic process eliminating UV-light induced DNA damaged cells, elucidating molecular events regulating apoptosis enhances understanding of cutaneous photocarcinogenesis. Here we demonstrate low-dose UV-light enhances susceptibility of KCs to TRAIL-induced apoptosis. Low-dose UV-light selectively reduces decoy receptors, without influencing death receptor levels. UV-induced enhanced apoptotic susceptibility was reduced by over-expression of decoy receptor TRAIL-R4, but not TRAIL-R3; or treatment with thiol compound pyrrolidine dithiocarbamate (PDTC), which also enhanced TRAIL-R4 levels. Besides influencing decoy receptors, low-dose UV-light plus TRAIL also synergistically promoted cytochrome c and Smac release from mitochondria. Inhibitors directed against caspases 2, 3, 8, and 9 reduced the synergistic apoptotic response following low-dose UV-light plus TRAIL exposure; as did forced over-expression of Bcl-x and dominant negative (DN) constructs of FADD and caspase 9. Thus, relative levels of decoy receptors significantly influence susceptibility of KCs to TRAIL-induced apoptosis with concomitant low-dose UV-light exposure; in addition to the apoptotic pathway mediated by mitochondrial permeabilization.
Authors:
Jian-Zhong Qin; Patricia Bacon; Jeffrey Panella; Leonid A Sitailo; Mitchell F Denning; Brian J Nickoloff
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  200     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-05-11     Completed Date:  2004-07-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  155-66     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Wiley-Liss, Inc.
Affiliation:
Department of Pathology, Loyola University Medical Center, Maywood, Illinois 60153, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Apoptosis Regulatory Proteins
Blotting, Western
Carrier Proteins / secretion
Caspases / antagonists & inhibitors,  metabolism
Cells, Cultured
Cytochromes c / secretion
Fluorescent Antibody Technique, Indirect
Humans
Intracellular Signaling Peptides and Proteins
Keratinocytes / cytology,  drug effects,  metabolism*,  radiation effects*
Luciferases / genetics
Male
Membrane Glycoproteins / metabolism*
Mitochondria / metabolism,  radiation effects
Mitochondrial Proteins / secretion
Penis / anatomy & histology
Proto-Oncogene Proteins c-bcl-2 / metabolism
Receptors, Tumor Necrosis Factor / metabolism
Retroviridae / genetics
Skin / cytology
TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha / metabolism*
Tumor Suppressor Protein p53 / metabolism
Ultraviolet Rays
bcl-X Protein
Grant Support
ID/Acronym/Agency:
AR47307/AR/NIAMS NIH HHS; AR47814/AR/NIAMS NIH HHS; CA83784/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/BCL2L1 protein, human; 0/Carrier Proteins; 0/DIABLO protein, human; 0/Intracellular Signaling Peptides and Proteins; 0/Membrane Glycoproteins; 0/Mitochondrial Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Receptors, Tumor Necrosis Factor; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFRSF10A protein, human; 0/TNFSF10 protein, human; 0/Tumor Necrosis Factor-alpha; 0/Tumor Suppressor Protein p53; 0/bcl-X Protein; 9007-43-6/Cytochromes c; EC 1.13.12.-/Luciferases; EC 3.4.22.-/Caspases

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