Non-erythroid alpha-spectrin breakdown by calpain and interleukin 1 beta-converting-enzyme-like protease(s) in apoptotic cells: Contributory roles of both protease families in neuronal apoptosis
Non-erythroid alpha-spectrin breakdown by calpain and interleukin 1 beta-converting-enzyme-like protease(s) in apoptotic cells: Contributory roles of both protease families in neuronal apoptosis
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DOI：
10.1042/bj3190683
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发表时间：
1996-11-01
影响因子：
4.1
通讯作者：
Wang, KKW
中科院分区：
文献类型：
--
作者：
Nath, R;Raser, KJ;Wang, KKW
细胞骨架蛋白非红细胞α-血影蛋白是一种内源性钙蛋白酶底物，特别是在病理生理条件下。在细胞坏死（例如，经maitotoxin处理的神经母细胞瘤SH-SY 5 Y细胞）中，细胞钙蛋白酶产生150 kDa和145 kDa的α-血影蛋白分解产物（SBDP）。相反，在经历细胞凋亡的神经元细胞（小脑颗粒神经元经受低钾和用星形孢菌素处理的SH-SY 5 Y细胞）中，还观察到120 kDa的额外SBDP。120 kDa SBDP的形成对钙蛋白酶抑制剂不敏感，但可被白细胞介素1 β转化酶（ICE）样蛋白酶抑制剂Z-Asp-CH 2 OC（O）-2，6-二氯苯完全阻断。在凋亡细胞中也观察到钙蛋白酶和ICE同系物CPP 32的自溶活化，α-Spectrin也可以在体外被纯化的钙蛋白酶切割以产生150/145 kDa的SBDP双联体，并被ICE和ICE同源物[ICH-1、ICH-2和CPP 32（β）]切割以产生150 kDa的SBDP，此外，CPP 32和ICE也产生120 kDa SBDP。此外，ICE样蛋白酶或钙蛋白酶的抑制保护颗粒神经元和SH-SY 5 Y细胞免于凋亡。我们的研究结果表明，这两个蛋白酶家族参与神经元凋亡的表达。
The cytoskeletal protein non-erythroid alpha-spectrin is well documented as an endogenous calpain substrate, especially under pathophysiological conditions. In cell necrosis (e.g. maitotoxin-treated neuroblastoma SH-SY5Y cells), a-spectrin breakdown products (SBDPs) of 150 kDa and 145 kDa were produced by cellular calpains. In contrast, in neuronal cells undergoing apoptosis (cerebellar granule neurons subjected to low potassium and SH-SY5Y cells treated with staurosporine), an additional SBDP of 120 kDa was also observed. The formation of the 120 kDa SBDP was insensitive to calpain inhibitors but was completely blocked by an interleukin 1 beta-converting-enzyme (ICE)-like protease inhibitor, Z-Asp-CH2OC(O)-2,6-dichloro-benzene, Autolytic activation of both calpain and the ICE homologue CPP32 was also observed in apoptotic cells, alpha-Spectrin can also be cleaved in vitro by purified calpains to produce the SBDP doublet of 150/145 kDa and by ICE and ICE homologues [ICH-1, ICH-2 and CPP32(beta)] to produce a 150 kDa SBDP, In addition, CPP32 and ICE also produced a 120 kDa SBDP. Furthermore inhibition of either ICE-like protease(s) or calpain protects both granule neurons and SH-SY5Y cells against apoptosis. Our results suggest that both protease families participate in the expression of neuronal apoptosis.