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基于天冬氨酸的白细胞介素-1β转化酶抑制剂可预防抗肿瘤药物诱导的人髓性白血病U937细胞凋亡。

Aspartate-based inhibitor of interleukin-1 beta-converting enzyme prevents antitumor agent-induced apoptosis in human myeloid leukemia U937 cells.

作者信息

Mashima T, Naito M, Kataoka S, Kawai H, Tsuruo T

机构信息

Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.

出版信息

Biochem Biophys Res Commun. 1995 Apr 26;209(3):907-15. doi: 10.1006/bbrc.1995.1584.

Abstract

We found that a novel protease inhibitor, benzyloxycarbonyl-Asp-CH2OC(O)-2,6-dichlorobenzene (Z-Asp-CH2-DCB), which can preferentially inhibit interleukin-1 beta-converting enzyme (ICE), completely blocked the apoptotic cell death of human myeloid leukemia U937 cells caused by etoposide, camptothecin, 1-beta-D-arabinofuranosyl-cytosine and Adriamycin, as well as TNF-alpha, anti-Fas antibody and staurosporine. However, Z-Asp-CH2-DCB did not block non-apoptotic cell death of U937 cells caused by etoposide during prolonged incubation periods. These results indicate that ICE or ICE-like proteases inhibited by Z-Asp-CH2-DCB are involved in a common pathway of apoptotic cell death in U937 cells.

摘要

我们发现一种新型蛋白酶抑制剂,苄氧羰基 - 天冬氨酸 - CH₂OC(O)-2,6 - 二氯苯(Z - Asp - CH₂ - DCB),它能优先抑制白细胞介素 - 1β转化酶(ICE),可完全阻断由依托泊苷、喜树碱、1 - β - D - 阿拉伯呋喃糖基胞嘧啶和阿霉素以及肿瘤坏死因子 - α、抗Fas抗体和星形孢菌素所引发的人髓性白血病U937细胞的凋亡性细胞死亡。然而,在延长的孵育期内,Z - Asp - CH₂ - DCB并未阻断依托泊苷所引发的U937细胞的非凋亡性细胞死亡。这些结果表明,被Z - Asp - CH₂ - DCB抑制的ICE或ICE样蛋白酶参与了U937细胞凋亡性细胞死亡的共同途径。

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