Ethylnitrosourea induces neural progenitor cell apoptosis after S-phase accumulation in a p53-dependent manner
Neural progenitor cells populate the ventricular zone of the fetal central nervous system. In this study, immediately after the administration of ethylnitrosourea (ENU), an alkylating agent, an accumulation of neural progenitor cells in the S phase was observed. This event was caused by the inhibiti...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2005-02-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996104002281 |
| _version_ | 1829470432909066240 |
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| author | Kei-ichi Katayama Masaki Ueno Hirofumi Yamauchi Takayuki Nagata Hiroyuki Nakayama Kunio Doi |
| author_facet | Kei-ichi Katayama Masaki Ueno Hirofumi Yamauchi Takayuki Nagata Hiroyuki Nakayama Kunio Doi |
| author_sort | Kei-ichi Katayama |
| collection | DOAJ |
| description | Neural progenitor cells populate the ventricular zone of the fetal central nervous system. In this study, immediately after the administration of ethylnitrosourea (ENU), an alkylating agent, an accumulation of neural progenitor cells in the S phase was observed. This event was caused by the inhibition or arrest of DNA replication rather than acceleration of the G1/S transition. Soon after this accumulation reached its peak, the number of cells in the G2/M phase decreased and the apoptotic cell count increased. In p53-deficient mice, both ENU-induced apoptosis and S-phase accumulation were almost completely abrogated. These findings indicate that ENU inhibits or arrests DNA replication in neural progenitor cells during the S phase and then evokes apoptosis before the cells enter the G2 phase. Furthermore, these data also demonstrate that both ENU-induced apoptosis and cell cycle perturbation in the S phase require p53. |
| first_indexed | 2024-12-14T01:45:19Z |
| format | Article |
| id | doaj.art-212f5e34b1a14dfe8bfc0f5c7739d599 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-14T01:45:19Z |
| publishDate | 2005-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-212f5e34b1a14dfe8bfc0f5c7739d5992022-12-21T23:21:35ZengElsevierNeurobiology of Disease1095-953X2005-02-01181218225Ethylnitrosourea induces neural progenitor cell apoptosis after S-phase accumulation in a p53-dependent mannerKei-ichi Katayama0Masaki Ueno1Hirofumi Yamauchi2Takayuki Nagata3Hiroyuki Nakayama4Kunio Doi5Corresponding author. Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. Fax: +81 3 5841 8185.; Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, JapanNeural progenitor cells populate the ventricular zone of the fetal central nervous system. In this study, immediately after the administration of ethylnitrosourea (ENU), an alkylating agent, an accumulation of neural progenitor cells in the S phase was observed. This event was caused by the inhibition or arrest of DNA replication rather than acceleration of the G1/S transition. Soon after this accumulation reached its peak, the number of cells in the G2/M phase decreased and the apoptotic cell count increased. In p53-deficient mice, both ENU-induced apoptosis and S-phase accumulation were almost completely abrogated. These findings indicate that ENU inhibits or arrests DNA replication in neural progenitor cells during the S phase and then evokes apoptosis before the cells enter the G2 phase. Furthermore, these data also demonstrate that both ENU-induced apoptosis and cell cycle perturbation in the S phase require p53.http://www.sciencedirect.com/science/article/pii/S0969996104002281ApoptosisCell cycle arrestDevelopmentDNA damageDNA replicationEthylnitrosourea |
| spellingShingle | Kei-ichi Katayama Masaki Ueno Hirofumi Yamauchi Takayuki Nagata Hiroyuki Nakayama Kunio Doi Ethylnitrosourea induces neural progenitor cell apoptosis after S-phase accumulation in a p53-dependent manner Neurobiology of Disease Apoptosis Cell cycle arrest Development DNA damage DNA replication Ethylnitrosourea |
| title | Ethylnitrosourea induces neural progenitor cell apoptosis after S-phase accumulation in a p53-dependent manner |
| title_full | Ethylnitrosourea induces neural progenitor cell apoptosis after S-phase accumulation in a p53-dependent manner |
| title_fullStr | Ethylnitrosourea induces neural progenitor cell apoptosis after S-phase accumulation in a p53-dependent manner |
| title_full_unstemmed | Ethylnitrosourea induces neural progenitor cell apoptosis after S-phase accumulation in a p53-dependent manner |
| title_short | Ethylnitrosourea induces neural progenitor cell apoptosis after S-phase accumulation in a p53-dependent manner |
| title_sort | ethylnitrosourea induces neural progenitor cell apoptosis after s phase accumulation in a p53 dependent manner |
| topic | Apoptosis Cell cycle arrest Development DNA damage DNA replication Ethylnitrosourea |
| url | http://www.sciencedirect.com/science/article/pii/S0969996104002281 |
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