Frequent nuclear localization of ICAD and cytoplasmic co‐expression of caspase‐8 and caspase‐3 in human lymphomas
Frequent nuclear localization of ICAD and cytoplasmic co‐expression of caspase‐8 and caspase‐3 in human lymphomas
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人淋巴瘤中 ICAD 的频繁核定位以及 caspase-8 和 caspase-3 的细胞质共表达
作者：
L. Xerri;F. Palmérini;E. Devilard;T. Defrance;R. Bouabdallah;J. Hassoun;F. Birg
淋巴瘤细胞通常在体外显示出对FAS诱导的细胞凋亡的抗性，其中半胱天冬酶作为关键的细胞死亡效应子。FAS刺激后，caspase-8激活caspase-3，caspase-3又通过其抑制剂（ICAD）的蛋白水解激活caspase-激活的DNA酶（CAD）。为了研究FAS耐药的机制，通过免疫组织化学分析了52例非霍奇金淋巴瘤（NHL）、12例霍奇金病（HD）和8例良性淋巴组织中caspase-8的表达，以及底物caspase-3和ICAD的表达。在良性组织中，caspase-8与caspase-3在生发中心（GC）细胞的细胞质中共表达，并与ICAD在外套和边缘区细胞的细胞核中共表达。GC细胞ICAD表达较弱或不表达。12例弥漫性大细胞B-NHL中有11例出现caspase-8和caspase-3的胞浆染色。在9/9个滤泡NHL、5/5个套细胞NHL和6/6个边缘区NHL中，Caspase-8阳性为细胞核和细胞质。六分之五的外周T细胞NHL表达细胞质caspase-8。12例HD病例中有10例在大多数Reed-Sternberg细胞中缺乏caspase-3和caspase-8的显著细胞质染色。所有淋巴瘤病例均表现出主要的核ICAD阳性。三个淋巴瘤样本和正常外套带细胞的亚细胞分级分析证实，ICAD和caspase-8至少部分位于细胞核中。这些结果表明，caspase-8的表达谱与组织学淋巴瘤亚型相关; caspase-8与caspase-3在GC细胞及其肿瘤对应物中共表达; ICAD在体内具有免疫组织化学核定位;并且caspase-8和ICAD可以在外套带和边缘带细胞的核中共表达;它们出乎意料的核定位允许重新评估胱天蛋白酶激活的生化级联反应。版权所有© 2000约翰威利父子有限公司。
Lymphoma cells often display in vitro resistance to FAS‐induced apoptosis, in which caspases act as crucial cell death effectors. Following FAS stimulation, caspase‐8 activates caspase‐3, which in turn activates the caspase‐activated DNAse (CAD) by proteolysis of its inhibitor (ICAD). To investigate the mechanism of FAS resistance, the expression of caspase‐8 was analysed by immunohistochemistry, together with that of the substrates caspase‐3 and ICAD, in 52 representative samples from non Hodgkin's lymphoma (NHL), 12 from Hodgkin's disease (HD), and eight benign lymphoid tissues. In benign tissues, caspase‐8 was co‐expressed with caspase‐3 in the cytoplasm in germinal centre (GC) cells and was co‐expressed with ICAD in the nuclei of the mantle and marginal zone cells. ICAD expression was weak or absent in GC cells. Cytoplasmic staining for both caspase‐8 and caspase‐3 was present in 11/12 cases of diffuse large cell B‐NHL. Caspase‐8 positivity was nuclear and cytoplasmic in 9/9 follicular NHLs, in 5/5 mantle cell NHLs and in 6/6 marginal zone NHLs. Five out of six peripheral T‐cell NHLs expressed cytoplasmic caspase‐8. Ten out of the 12 HD cases lacked significant cytoplasmic staining for caspase‐3 and caspase‐8 in the majority of Reed–Sternberg cells. All lymphoma cases exhibited predominant nuclear ICAD positivity. Subcellular fractionation analysis of three lymphoma samples and normal mantle zone cells confirmed that ICAD and caspase‐8 were at least partly localized in the nucleus. These results show that the profile of caspase‐8 expression is correlated with histological lymphoma subtypes; that caspase‐8 is co‐expressed with caspase‐3 in GC cells and their neoplastic counterparts; that ICAD has an immunohistochemical nuclear localization in vivo; and that caspase‐8 and ICAD can be co‐expressed in the nuclei of mantle zone and marginal zone cells; their unexpected nuclear localization allows a reappraisal of the biochemical cascade of caspase activation. Copyright © 2000 John Wiley & Sons, Ltd.
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凋亡核酸酶的 ICAD/DFF 调节剂是核。
影响因子：
3.7
作者：
Samejima,K;Earnshaw,WC
通讯作者：
Earnshaw,WC
DOI：
10.1016/s0021-9258(18)47344-9
发表时间：
1994-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
T. Fernandes‐Alnemri;G. Litwack;E. Alnemri
通讯作者：
T. Fernandes‐Alnemri;G. Litwack;E. Alnemri
影响因子：
16
作者：
Yang, XL;Chang, HY;Baltimore, D
通讯作者：
Baltimore, D
影响因子：
20.3
作者：
Martins, LM;Mesner, PW;Kaufmann, SH
通讯作者：
Kaufmann, SH