Oxygen-stress induced gene expression in the perinatal lung of rats
| Project/Area Number |
12470216
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Tokyo University of Pharmacy Life Science |
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Principal Investigator |
TAKAHASHI Yuji Tokyo University of Pharmacy and Life Science School of Life Science Professor, 生命科学部, 教授 (20154875)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Shigeru Tokyo University of Pharmacy and Life Science School of Life Science Research Associate, 生命科学部, 助手 (10266900)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | stress response / CREB / ATF / Transcription Factor / fetus / oxygen stress / hyperosmotic stress / Bax inhibitor-1 / DANCE / ストレス応答反応 / BAX / アポトーシス / Nrf-2 |
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| Research Abstract |
In this research project, we hypothesized that the oxygen stress in the perinatal period may be the key regulator that controls the reorganization of lung tissue after birth. We focus our interest in the exploration of the function ATF5 and Bax Inhibitor-1
We identified Bax inhibitor-1, BI-1, as a developmentally regulated gene product in perinatal lung using suppressive subtractive hybridization. BI-1 is a novel suppressor of apoptosis. The developmental regulation of BI-1 in the late fetal and early postnatal lung is specific for P2, indicating that these two TATA-less promoters are differentially regulated in adult testis and developing lung. Since Bax inhibitor-1 functions as a suppressor of apoptosis, its expression could provide a survival advantage for select cell populations during the peak period of apoptosis that occurs at birth
We cloned ATF5 as the oxygen-stress induced gene. ATF5 is up-regulated by hyperoxia in vivo as well as in vitro. In cell culture system, deficiency of glutamine enhanced the level of the ATF5 mRNA. However, hyperosmotic stress down-regulated the ATF5 gene expression. Anti-ATF5 peptide antibody was made and applied to detect intracellilar localization in the lungcell. ATF5 localized in the uncleous under the control condition, but in the cytoplasm under the hyperosmotic condition. These results indicate that ATF5 is a stress-regulated gene ATF5
Both ATF5 and Bax inhibitor-1 have anti-apoptotic activity. Therefore, stress induced by birth affect the gene expression of these genes and regulated apoptosis and reorganization of lung after birth
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Report
(4 results)
Research Products
(7 results)
