文章基本信息

标题：Apoptosis of NG108-15 Cells Induced by Buprenorphine Hydrochloride Occurs via the Caspase-3 Pathway
本地全文：下载
作者：Fumihiko KUGAWA ; Akemichi UENO ; Masatada AOKI 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2000
卷号：23
期号：8
页码：930-935
DOI：10.1248/bpb.23.930
出版社：The Pharmaceutical Society of Japan
摘要：Apoptosis of NG108-15 neuroblastoma×glioma hydrid cells (NG108-15 cells) is induced by a morphine alkaloid derivative, buprenorphine hydrochloride (Bph). In a previous report, we used various apotosis inhibitors to identify the "death pathway", and found that caspase inhibitors Ac-YVAD-CHO (Ac-Yyr-Val-Ala-Asp-CHO) and Ac-DEVD-CHO (Ac-Asp-Glu-Val-Asp-CHO) did not inhibit this particular apoptosis. Here we tested ZAVD-FMK (Z-Val-Ala-Asp[OMe]-CH₂F) and Z-DEVD-FMK (Z-Asp[OMe]-Glu-[OMe]Val-Asp[OMe]-CH₂F) for their ability to inhibit Bph-induced NG108-15 apoptosis. These tri- or tetra-peptide caspase inhibitors have a fluoromethyl ketone in their C-terminus instead of an aldehyde, and thus are more permeable than Ac-YVAD-CHO and AC-DEVD-CHO. Our observations DNA ladder formatin, cell morphology changes, and caspase-3 activities all indicated that these cell membrane-permeable caspase inhibitors completely inhibited the apoptosis, providing strong evidince that this apoptosis occurs through the caspase cascade "death pathway." Our previous report also showed that pretreatment of NG108-15 cells with TPCK (N-tosyl-L-phenylalanyl chloromethyl ketone) prevented DNA fragmentation and decreased the cell viability in Bph-induced apoptosis. The comparsion of caspase-3 activities in Bph-induced samples with or without TPCK pretreatment revealed that caspase-3 was activated in both samples. Taken together, these results indicate that the Bph-induced apoptosis of NG-108-15 cells occurs via the conventional caspase-dependent death pathway and that TPCK pretreatment results in a DNA ladder-deficient apoptosis.
关键词：NG108-15;buprenorphine hydrochloride;apoptosis;caspase-3;TPCK (N-tosyl-L-phenylalanyl chloromethyl ketone)