Oxygen-stress induced gene expression in the perinatal lung of rats

氧应激诱导大鼠围产期肺基因表达

• 批准号: 12470216
• 负责人: TAKAHASHI Yuji
• 金额: $ 3.2万
• 依托单位: Tokyo University of Pharmacy Life Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470216/
• 关键词: 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

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-1We 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 birthWe 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 ATF5Both 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

在这个研究项目中，我们假设围产期的氧应激可能是控制出生后肺组织重组的关键调节因子。我们的兴趣集中在探索 ATF5 和 Bax Inhibitor-1 的功能上。我们使用抑制性消减杂交技术，将 Bax Inhibitor-1（BI-1）确定为围产期肺部的发育调节基因产物。 BI-1 是一种新型的细胞凋亡抑制剂。 BI-1 在胎儿晚期和出生后早期肺中的发育调节对 P2 具有特异性，表明这两个 TATA-less 启动子在成人睾丸和发育中的肺中受到差异性调节。由于 Bax 抑制剂-1 起到细胞凋亡抑制因子的作用，因此其表达可以为出生时发生的细胞凋亡高峰期的选定细胞群提供生存优势。我们将 ATF5 克隆为氧应激诱导基因。 ATF5 在体内和体外都会因高氧而上调。在细胞培养系统中，谷氨酰胺的缺乏会增强 ATF5 mRNA 的水平。然而，高渗应激下调了 ATF5 基因的表达。制备抗ATF5肽抗体并应用于检测肺细胞的细胞内定位。在对照条件下ATF5定位于细胞质，而在高渗条件下定位于细胞质。这些结果表明ATF5是应激调节基因ATF5，ATF5和Bax抑制剂-1均具有抗凋亡活性。因此，出生引起的应激会影响这些基因的表达，并调节出生后肺的细胞凋亡和重组。

项目成果

Takahashi, S., Dohi, N., Takahashi, Y., Miura, T.: "Cloning and characterization of the 5'-flanking region of the rat p4Halpha gene encoding the prolyl 4-hydroxylase alpha(I) subunit(1)."Biochim Biophys Acts.. 1574(3). 354-358 (2002)

Takahashi, S.、Dohi, N.、Takahashi, Y.、Miura, T.：“编码脯氨酰 4-羟化酶 α(I) 亚基的大鼠 p4Halpha 基因 5 侧翼区域的克隆和表征 (1)

高橋 勇二, 三浦 卓: "低酸素応答によるCREB-CBPの機能"医学のあゆみ. 203. 531-534 (2002)

Yuji Takahashi、Takashi Miura：“低氧反应对 CREB-CBP 的作用”《医学史》203. 531-534 (2002)。

Takahashi S., Takahashi Y.: "Co-operation of the transcription factor hepatocyte nuclear factor-4 with Sp1 or Sp3 leads to transcriptional activation of the human haem oxygenase-1 gene promoter in a hepatoma cell line"Biochemical Journal. 367. 641-652 (20

Takahashi S.、Takahashi Y.：“转录因子肝细胞核因子 4 与 Sp1 或 Sp3 的合作导致肝癌细胞系中人血红素加氧酶 1 基因启动子的转录激活”《生化杂志》。

Hirono Y., Takahashi T.: "Prolonged hypoxia accelerates the pottranscriptional process of collagen synthesis in cultured fibroblasts"Life Science. 71. 3031-3045 (2002)

Hirono Y.、Takahashi T.：“长期缺氧会加速培养成纤维细胞中胶原蛋白合成的转录过程”生命科学。

Horino Y., Takahashi S., Miura T., Takahashi Y.: "Prolonged hypoxia accelerates the posttranscriptional process of collagen synthesis in cultured fibroblasts."Life Sci.. 71(26). 3031-3045 (2002)

Horino Y.、Takahashi S.、Miura T.、Takahashi Y.：“长期缺氧会加速培养成纤维细胞中胶原蛋白合成的转录后过程。”Life Sci.. 71(26)。