Mechanism and function of apoptosis

细胞凋亡的机制和功能

• 批准号: 06045054
• 负责人: TANUMA Sei-ichi
• 金额: $ 3.71万
• 依托单位: Science University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 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-06045054/
• 关键词: apoptosis; DNA fragmentation; DNA endonuclease; DNase gamma; cell death; エンドヌクレアーゼ; 神経細胞死; 神経変性疾患; 多発性硬化症; 胸腺細胞

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 suicide is regulated and why DNA is cleaved. Here, we found that gamma type of DNase was retained in apoptotic rat thymocyte nuclei. The mode of DNA cleavage, 3'-hydroxyl (OH) /5'-phosphoryl (P) ends, by homogeneously purified DNase gamma (Mr=33 kDa) 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.

细胞凋亡是多细胞生物从细胞群落中清除不需要细胞的一种机制。细胞凋亡调控的异常可能在癌症、自身免疫性疾病、艾滋病、退行性神经疾病和畸形的病因学中发挥作用。细胞凋亡的标志之一是基因组DNA的酶裂解成核小体低聚物。鉴定一种负责细胞凋亡的内切酶可能有助于解释这种细胞自杀是如何被调节的以及为什么DNA被切割。在这里，我们发现凋亡的大鼠胸腺细胞核中保留了γ型dna酶。同源纯化的DNase γ (Mr=33 kDa)切割3′-羟基(OH) /5′-磷酸基(P)端DNA的模式及其Zn^<2+>敏感性与辐照或糖皮质激素治疗诱导胸腺细胞凋亡的模式一致，表明该内切酶是胸腺细胞凋亡机制的核心组成部分。

项目成果

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)。

Yoshio Ueno, Kiyoko Umemori, Ei-ich Niimi, Sei-ichi Tanuma, Satoru Nagata, Masao Sugamata, Tomomi Ihara, Masaru Sekijima, Ken-ichi Kawai, Ikuko Ueno, and Fumio Tashiro: "Induction of apoptosis by T2 toxin and other natural toxins in HL-60 human promyeloti

Yoshio Ueno、Kiyoko Umemori、Ei-ich Niimi、Sei-ichi Tanuma、Satoru Nagata、Masao Sugamata、Tomomi Ihara、Masaru Sekijima、Ken-ichi Kawai、Ikuko Ueno 和 Fumio Tashiro：“T2 毒素和其他天然毒素诱导细胞凋亡

Daisuke Shiokawa, Kazunari, Nishimura, Hidieharu Maruta, and Sei-ichi Tanuma: "DNA fragmentation during thymic apoptosis is catalyzed by DNase gamma." Apoptosis. 1. 147-152 (1996)

Daisuke Shiokawa、Kazunari、Nishimura、Hidieharu Maruta 和 Sei-ichi Tanuma：“胸腺细胞凋亡过程中的 DNA 断裂是由 DNase gamma 催化的。”

Sei-ichi Tanuma: "Occurence of an NAD+ glycohydrolase in bovine brain cytosol." Arch.Biochem.Biophys.308. 327-329 (1994)

Sei-ichi Tanuma：“牛脑细胞质中 NAD 糖水解酶的存在。”

Sei-ichi: "DNA fragmentation in apoptosis." Tiss.Cult.Res.Commun.53. 1-9 (1995)

Sei-ichi：“细胞凋亡中的 DNA 碎片。”