Molecular mechanisms and function of apoptosis Faculty of Pharmaceutical Science

细胞凋亡的分子机制和功能 药学院

• 批准号: 06454679
• 负责人: TANUMA Sei-ichi
• 金额: $ 3.9万
• 依托单位: Science University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06454679/
• 关键词: apoptpsis; DNA fragmentation; DNA endonuclease; DNase gamma; cell death; ネクローシス; DNA分断化; ヌクレオソーム; DNaseγ; 胸腺細胞; プログラム細胞死

Apoptosis is a mechanism for eliminating unwanted cells from the cell community of multicellular organisms. Abnormalities in the regulation of apoptosis may play a part in the aetiology of cancer, autoimmune diseases, AIDS,degenerative nerve diseases and malformation. On of the hallmarks of apoptosis is the enzymatic cleavage of genomic DNA into nucleosomal oligomers. The identification of an endonuclease responsible for apoptosis might help to explain how this cell suiside is regulated and why DNA is cleaved. Here, we found that gamma type of DNase was retained in apoptptic rat thymocyte nuclei. The mode of DNA cleavage, 3'-hydroxyl (OH) /5'-phosphoryl (P) ends, by homogeneously purified DNase gamma (Mr=33kDa) and its Zn^<2+> sensitivity match those observed in apoptosis in thymocytes induced by irradiation or glucocorticoid treatment, indicating that this endonuclease is a central component of the thymic apoptosis machinery.

细胞凋亡是从多细胞生物的细胞群落中清除不需要的细胞的机制。细胞凋亡调控异常可能在肿瘤、自身免疫性疾病、艾滋病、神经退行性疾病和畸形等疾病的发病机制中起一定作用。细胞凋亡的标志之一是基因组DNA酶促裂解成核小体寡聚体。鉴定负责细胞凋亡的核酸内切酶可能有助于解释这种细胞凋亡是如何调节的，以及为什么DNA被切割。在此，我们发现γ型DNA酶保留在胸腺细胞核中。DNA酶γ（Mr= 33 kDa）的DNA切割模式（3 '-羟基（OH）/5'-磷酰基（P）末端）及其对Zn^<2+>的敏感性与辐射或糖皮质激素处理诱导的胸腺细胞凋亡中观察到的一致，表明这种核酸内切酶是胸腺细胞凋亡机制的核心成分。

项目成果

F.Uchiumi, T.Ohta, and S.Tanuma: "Replication factor C recognizes 5'-phosphate ends of telomeres" Biochem.Biophys.Res.Commun.229. 310-315 (1996)

F.Uchiumi、T.Ohta 和 S.Tanuma：“复制因子 C 识别端粒的 5-磷酸末端”Biochem.Biophys.Res.Commun.229。

S.Tanuma: "In Apoptosis in Normal Development and Cancer (ed.by Mels Sluyser), Taylor & Francis Ltd., London UK" Molecular mechanisms of apoptosis. 39-59 (1996)

S.Tanuma：“正常发育和癌症中的细胞凋亡（Mels Sluyser 编辑），Taylor

Sei-ichi Tanuma: "DNA fragment'ation during thymic apoptosis is catalyzed by DNaseγ." Apoptosis. 1. 147-152 (1996)

Sei-ichi Tanuma：“胸腺细胞凋亡过程中的 DNA 片段化是由 DNaseγ 催化的。” 1. 147-152 (1996)。

Shiokawa, D.et al: "Identification of an endonuclease responsible for apoptosis in rat thymocytes." Eur.J.Biochem. 226. 23-30 (1994)

Shiokawa, D. 等人：“鉴定负责大鼠胸腺细胞凋亡的核酸内切酶。”

Sei-ichi Tanuma: "Molecular mechanisms of apoptosis." Apoptosis in Normal Development and Cancer (ed.by Mels Sluyser). Taylor & Francis. 39-59 (1996)

Sei-ichi Tanuma：“细胞凋亡的分子机制。”