神经
词汇介绍
拓展阅读
解析
caspase
释 义 n. 半胱天冬酶；切冬酶（胱冬肽酶）；细胞凋亡蛋白酶
例 句 The inflammasomes join together and activate a protein, caspase-1, that in turn triggers an inflammatory response. 这些炎症小体联合起来可以激活半胱天冬酶-1，这种蛋白依次激活炎症的级联反应。
概述
概述
也称半胱天冬酶，细胞凋亡蛋白酶分为启动型和执行型，前者接受死亡信号、启动凋亡或激活下游的分子，后者则降解细胞骨架、蛋白质、核酸等。半胱天冬酶如何启动和实施凋亡、受哪些因素调节等问题是近年来生命科学研究领域的热点之一。
两条激活途径
细胞外途径：胞外配体与胞膜受体结合后，衔接蛋白作为一个平台，提供场所给上游前半胱天冬酶-8完成聚合及相互剪切之用。前半胱大冬酶-8与受体蛋白结合后，同受体一起形成凋亡体，前半胱天冬酶间的聚合需要依赖其前区的两种特殊结构：DED区和CARD区。
细胞内途径：细胞凋亡启动后，Bax蛋白由胞液转移至线粒体膜上，在此构建膜孔或裂隙。细胞色素c从构建的孔隙中进入胞液，在dATP的协助下，结合Apaf-1的C端WD重复区，它们共同使前半胱天冬酶-9转变为半胱天冬酶-9。
半胱天冬酶临床应用前景
Moskowitz和Yuan等的实验表明，在缺氧导致的脑细胞死亡中，半胱天冬酶扮演了重要的角色。另外，细胞癌变除了因为遗传物质的突变以外，凋亡信号转导通路发生异常也是重要因素之一。一些肿瘤细胞会产生一种诱骗受体DcR3，它阻止了FasL与Fas的结合，而化疗的无效往往就是因为受体或凋亡相关蛋白发生改变，死亡信号不能顺利继续传递所致。这提示在临床治疗上是否能够运用某些药物,绕过病变环节而直接作用于下游分子以达到治疗的目的。
Hsp60 and IL-8 axis promotes apoptosis resistance in cancer
复制标题
Hsp60和IL-8轴促进肿瘤细胞凋亡抵抗
发表时间：2019-11-01
影响指数：5.4
作者： Sandeep Kumar
期刊：Br J Cancer
BACKGROUND: Interleukin-8 (IL-8) and heat shock protein 60 (Hsp60) play crucial roles in cell survival and maintenance of cellular homoeostasis. However, cross talks between these two proteins are not defined.METHODS: IL-8 expression in tumour tissue sections was analysed by immunohistochemistry. IL-8 expression and release in cancer cells was quantified using enzyme-linked immunosorbent assay (ELISA). Apoptosis was quantified using caspase activity and Annexin-V/PI staining.RESULTS: We observed IL-8 release from cancer cells in response to histone deacetylase inhibitor, apicidin (Api), and non-competitive inhibitor of the sarco/endoplasmic reticulum Ca ATPase, thapsigargin (TG). IL-8 release was increased upon TG-treatment. TG-induced IL-8 expression was reduced in the presence of Api in Bax-dependent manner. Increased apoptosis was associated with decreased IL-8 expression in response to combined treatment of TG and Api. TG and Api combination induced caspase-8 and caspase-9 dependent apoptosis. Hsp60 knockdown abrogated IL-8 expression induced by Api, TG, and their combination. The level of TGF-β, an upstream regulator of IL-8, was decreased upon Hsp60-silencing. Knocking down Hsp60 decreased IL-8 expression and its release in prostate cancer cell xenograft tumours in SCID mice.CONCLUSION: This study describes the underlying mechanism associated with apoptosis resistance mediated via Hsp60-IL-8 axis in cancer.
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