The role of reduced expression of glutathione peroxidase gene on the development and progression of hepatocellular carcinoma

谷胱甘肽过氧化物酶基因表达降低在肝细胞癌发生、发展中的作用

• 批准号: 07457065
• 负责人: MORIUCHI Tetsuya
• 金额: $ 4.8万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457065/
• 关键词: LEC rat; p53; glutathione peroxidase; hepatitis; グルタチオン・ベルオキシダーゼ

The Long-Evans Cinnamon (LEC) rat is a mutant strain in which hepatitis and liver cancer spontaneously develop at extremely high rates. We observed marked reduction in the activity of cellular glutathione peroxidase (GSH-Px) in the liver of LEC rats and p53 knockout mice. To determine whether GSH-Px promoter is activated by p53, liciferase assay was performed. Activation of GSH-Px promoter was found in both cell llines expressing wild-type p53 and mutant p53, indicating that GSH-Px promoter is activated by N-terminal activation domain of p53. To investigate the role of selenium-dependent GSH-Px in the development of hereditary hepatitis, we compared incidences and grades of acute hepatitis between the LEC rats fed with seleniumm-supplemented diet and selenium-deficient diet. We found that selenium-deficient status and resultant GSH-Px deficiency does not promote hepatitis but rather have an inhibitory effect on the development of hepatitis in LEC rats.

Long-Evans Cinnamon（LEC）大鼠是一种突变品系，其中肝炎和肝癌以极高的速率自发发展。我们观察到LEC大鼠和p53基因敲除小鼠肝脏细胞谷胱甘肽过氧化物酶（GSH-Px）活性显著降低。为了确定GSH-Px启动子是否被p53激活，进行liciferase测定。GSH-Px启动子在野生型和突变型p53细胞中均被激活，表明GSH-Px启动子受p53 N端激活结构域的激活。为探讨硒依赖型谷胱甘肽过氧化物酶（GSH-Px）在遗传性肝炎发病中的作用，我们比较了补硒和缺硒饲料喂养的LEC大鼠急性肝炎的发病率和分级。我们发现，硒缺乏的状态和由此产生的GSH-Px缺乏症并不促进肝炎，而是有抑制作用的LEC大鼠肝炎的发展。

项目成果

守内 哲也: "Possible roles of an adult T cell leukemia-derived factor (ADF) /thioredoxin in drug resistance of adult T cell leukemia (ATL) to Adriamycin" Blood. (印刷中).

Tetsuya Moriuchi：“成人 T 细胞白血病衍生因子 (ADF)/硫氧还蛋白在成人 T 细胞白血病 (ATL) 对阿霉素耐药中的可能作用”血液（正在出版）。

守内哲也: "Cloning, sequencing, and chromosomal localization of two tandemly arranged human pseudogenes for the proliferating cell nuclear antigen (PCNA)." Mamm. Genome. 7. 906-908 (1996)

Tetsuya Moriuchi：“增殖细胞核抗原 (PCNA) 的两个串联排列的人类假基因的克隆、测序和染色体定位。Mamm。”

守内哲也: "Plasma glutathione peroxidase deficiency caused by renal dysfunction." Nephron. 73. 207-211 (1996)

Tetsuya Moriuchi：“肾功能障碍引起的血浆谷胱甘肽过氧化物酶缺乏。”73. 207-211 (1996)

守内哲也: "Overexpression of the HOX4A (HOXD3) homerobox gene in human erythroleukemie HEL cells results in altered adhesive properties." Blood. 85. 2786-2794 (1995)

Tetsuya Moriuchi：“人红白血病 HEL 细胞中 HOX4A (HOXD3) 同源框基因的过度表达导致血液粘附特性改变。”

守内哲也: "新病理学総論" 南山堂(印刷中), 15

森内哲也：《病理学新通论》Nanzando（出版中），15