Involvement of p53 and Fas CD95 in murine neural progenitor cell response to ionizing irradiation

We investigated the role of tumor suppressor p53 and Fas (CD95/APO-1), a member of the tumor necrosis factor receptor family, in neural progenitors response to gamma-irradiation exposure. Telencephalic cells were obtained from wild-type C57Bl/6, or p53-/- or fas-/-, 15-day-old mouse embryos. They we...

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Bibliographic Details
Published in:	Oncogene Vol. 23; no. 52; pp. 8497 - 8508
Main Authors:	SEMONT, Alexandra, NOWAK, Ewa B, SILVA LAGES, Céline, MATHIEU, Céline, MOUTHON, Marc-André, MAY, Evelyne, ALLEMAND, Isabelle, MILLET, Pascal, BOUSSIN, Francois D
Format:	Journal Article
Language:	English
Published:	Basingstoke Nature Publishing 04-11-2004 Nature Publishing Group
Subjects:	Ageing, cell death Animals Apoptosis Apoptosis - physiology Apoptosis - radiation effects Biological and medical sciences CD95 antigen Cell cycle Cell Cycle - physiology Cell Cycle - radiation effects Cell death Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cyclin-dependent kinase inhibitor p21 Embryos fas Receptor - metabolism Fundamental and applied biological sciences. Psychology Gamma Rays Gene expression Ionizing radiation Localization Mice Molecular and cellular biology Monoclonal antibodies Nervous system Neural stem cells Neurospheres p53 Protein Progenitor cells Radiation Receptors, Tumor Necrosis Factor - metabolism Signal transduction Signal Transduction - physiology Stem cells Stem Cells - metabolism Stem Cells - radiation effects Telencephalon Tumor necrosis factor-TNF Tumor suppressor genes Tumor Suppressor Protein p53 - metabolism γ Radiation France Ionizing irradiation TP53 Gene Fas/CD95 radiation neural progenitor Carcinogenesis Apoptosis Tumor suppressor gene p53
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Summary:	We investigated the role of tumor suppressor p53 and Fas (CD95/APO-1), a member of the tumor necrosis factor receptor family, in neural progenitors response to gamma-irradiation exposure. Telencephalic cells were obtained from wild-type C57Bl/6, or p53-/- or fas-/-, 15-day-old mouse embryos. They were cultured in conditions allowing neural progenitors to form proliferating clusters (neurospheres). A 2 Gy gamma-irradiation induced a G1 cell cycle arrest and triggered apoptosis in wild-type neural progenitor cultures in correlation with an enhanced expression of p53 and of its downstream target p21(WAF1), both of them acquiring a nuclear localization. These effects did not occur in p53-/- neural progenitors demonstrating the central role played by p53 in their response to ionizing radiation. Furthermore, the monoclonal antibody Jo2 directed against Fas induced apoptosis of wild type but not of fas-/- neural progenitors, indicating the existence of a functional Fas signaling pathway in neural progenitors. Ionizing radiation induced an increase of Fas membrane expression related to a p53-dependent increase of fas mRNA expression in wild-type neural progenitors. Moreover, fas-/- neural progenitors exhibited delayed radiation-induced apoptosis compared to wild-type cells. Therefore, these findings establish a role for Fas/CD95 related to p53 in the response of neural progenitors to gamma-radiation exposure. Similar mechanisms could be triggered in neural progenitors in case of different stresses during brain development or in the course of various diseases affecting the adult brain.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0950-9232 1476-5594
DOI:	10.1038/sj.onc.1207821