在I型白血病细胞中，由试验诱导的细胞凋亡不会因bax的过表达而增强。

Trail-induced apoptosis in Type I leukemic cells is not enhanced by overexpression of bax.

作者信息

Jia L, Patwari Y, Kelsey S M, Newland A C

机构信息

Department of Haematology/Oncology, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Turner Street, London, E1 2AD, United Kingdom.

出版信息

Biochem Biophys Res Commun. 2001 May 25;283(5):1037-45. doi: 10.1006/bbrc.2001.4895.

DOI:10.1006/bbrc.2001.4895

PMID:11355877

Abstract

We have previously shown that Bax translocation was crucial in TNFalpha or etoposide-induced apoptosis. Overexpression of Bax sensitized chronic myeloid leukemic K562 cells to etoposide-induced apoptosis. Treatment with TNF-related apoptosis-inducing ligand (TRAIL) induces a loss of mitochondrial membrane potential (DeltaPsim), cytochrome c release from mitochondria, activation of caspases-8, -9, and -3, and cleavage of Bid in the K562 cell line. Bax failed to sensitize K562 cells to TRAIL-induced apoptosis. TRAIL did not induce Bax expression and/or translocation from cytosol to mitochondria in the K562 cell line. However, 100 microM Z-VAD.fmk, a pan caspase inhibitor, completely blocked TRAIL-initiated mitochondrial alterations and cleavages of caspases and Bid. We propose that TRAIL-induced apoptosis in K562 cells is via Type I apoptotic signal pathway. Bax translocation is not essential for TRAIL-induced cytochrome c release and DeltaPsim collapse in the Type I cells.

摘要

我们之前已经表明，Bax转位在肿瘤坏死因子α（TNFα）或依托泊苷诱导的细胞凋亡中至关重要。Bax的过表达使慢性髓性白血病K562细胞对依托泊苷诱导的细胞凋亡敏感。用肿瘤坏死因子相关凋亡诱导配体（TRAIL）处理可导致K562细胞系中线粒体膜电位（ΔΨm）丧失、细胞色素c从线粒体释放、半胱天冬酶-8、-9和-3激活以及Bid裂解。Bax未能使K562细胞对TRAIL诱导的细胞凋亡敏感。在K562细胞系中，TRAIL未诱导Bax表达和/或从细胞质转位至线粒体。然而，100微摩尔的Z-VAD.fmk（一种泛半胱天冬酶抑制剂）完全阻断了TRAIL引发的线粒体改变以及半胱天冬酶和Bid的裂解。我们提出，TRAIL诱导K562细胞凋亡是通过I型凋亡信号通路。在I型细胞中，Bax转位对于TRAIL诱导的细胞色素c释放和ΔΨm崩溃并非必不可少。