Lactacystin, a specific inhibitor of the proteasome, induces apoptosis in human monoblast U937 cells
Lactacystin, a specific inhibitor of the proteasome, induces apoptosis in human monoblast U937 cells
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DOI：
10.1006/bbrc.1995.2878
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发表时间：
1995-12-26
影响因子：
3.1
通讯作者：
Kikuchi, H
中科院分区：
文献类型：
--
作者：
ImajohOhmi, S;Kawaguchi, T;Kikuchi, H
Lactacystin最初是从一种微生物中分离出来的神经生成诱导剂，靶向蛋白酶体的催化β亚基，并阻止细胞周期。在这里，我们首次报道了乳酸菌素诱导人单细胞U937细胞的凋亡细胞死亡。U937细胞经lactacystin培养后，细胞核萎缩，呈典型的凋亡形态变化，细胞活力下降。电泳分析显示，乳系统素处理细胞的染色体DNA在核体间呈阶梯状切割，表明细胞死亡是通过凋亡过程发生的，流式细胞术DNA片段分析也证实了这一点。这些发现表明，在增殖过程中抑制蛋白酶体可导致凋亡细胞死亡，蛋白酶体是细胞周期过程中决定细胞增殖、分化或死亡的关键酶。(C) 1995学术出版社，Inc。
Lactacystin, originally isolated from a microbe as an inducer of neuritogenesis, targets the catalytic beta-subunit of the proteasome, and arrests the cell cycle. Here we report for the first time that lactacystin induces apoptotic cell death in human monoblastic U937 cells. When U937 cells were cultured with lactacystin, their nuclei were shrunken, a morphological change typical of apoptosis, and cell viability was decreased. Electrophoretic analysis revealed that chromosomal DNAs from lactacystin-treated cells were cleaved in an internucleosomal ladder-like pattern, indicating that cell death occurs through an apoptotic process, which was also confirmed by DNA fragmentation analysis using flow cytometry. These findings suggest that inhibition of the proteasome during proliferation results in apoptotic cell death, and that the proteasome is a key enzyme in the course of the cell cycle that destines the cell to proliferate, differentiate or die. (C) 1995 Academic Press, Inc.