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首页> 外文期刊>Journal of cellular biochemistry. >Stress protein GRP78 prevents apoptosis induced by calcium ionophore, ionomycin, but not by glycosylation inhibitor, tunicamycin, in human prostate cancer cells.
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Stress protein GRP78 prevents apoptosis induced by calcium ionophore, ionomycin, but not by glycosylation inhibitor, tunicamycin, in human prostate cancer cells.

机译：应激蛋白GRP78可以阻止钙离子载体离子霉素诱导的凋亡，但不能阻止糖基化抑制剂衣霉素抑制人前列腺癌细胞的凋亡。

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摘要

GRP78 induction has recently been shown to play a critical role in maintaining cell viability against several kinds of stress, including depletion of endoplasmic reticulum Ca(2+) and accumulation of unglycosylated proteins, under specific experimental conditions. However, the functional significance of GRP78 induction after stressful treatment has not been well defined. This article characterizes the different biological features associated with GRP78 induction by two kinds of stress agents, calcium ionophore, ionomycin (IM), and glycosylation inhibitor, tunicamycin (TM), focusing on the association with apoptosis in human prostate cancer cells. Both IM and TM treatment resulted in marked induction of GRP78 transcription in androgen-dependent prostate cancer LNCaP cells maintained in medium without androgen, but not in medium containing androgen, as measured by Northern blotting and nuclear run-off assays. After pretreatment with tumor necrosis factor-alpha, which has potent cytotoxic effects on LNCaP cells, both IM and TM could induce substantial increases in GRP78 transcription in LNCaP cells, even in medium containing androgen. Under both experimental conditions described, DNA fragmentation assays showed a direct correlation between the onset of apoptosis in LNCaP cells after IM treatment and the initiation of GRP78 transcript induction, while induction of GRP78 expression preceded TM-induced apoptosis. To elucidate the functional differences of GRP78 induction by IM and TM, an antisense oligodeoxynucleotide (ODN) targeted against the grp78 gene was designed to reduce GRP78 expression in a sequence-specific and dose-dependent manner. Antisense GRP78 ODN treatment substantially enhanced apoptosis of LNCaP cells induced by IM compared with mismatch control ODN treatment, whereas no marked differences were observed in apoptotic features induced by TM with antisense GRP78 and mismatch control ODN treatment. Studies of additional androgen-independent prostate cancer PC3 cells also demonstrated a correlation between GRP78 induction and resistance to apoptosis after IM treatment, but not after TM treatment. These findings suggest that there are at least two GRP78 signaling pathways, which play different roles in resistance against stress-induced apoptosis. Copyright 2000 Wiley-Liss, Inc.
机译：最近显示GRP78诱导在维持细胞活力以抵抗几种压力，包括在内质网Ca（2+）耗尽和未糖基化蛋白的积累，在特定的实验条件下的关键作用。但是，应激治疗后GRP78诱导的功能意义尚未明确。本文描述了两种应激因子（钙离子载体，离子霉素（IM）和糖基化抑制剂，衣霉素（TM））与GRP78诱导相关的不同生物学特征，重点研究了与人类前列腺癌细胞凋亡的相关性。如通过RNA印迹和核径流试验所测量的，IM和TM处理均导致在雄激素依赖性前列腺癌LNCaP细胞中显着诱导GRP78转录，所述LNCaP细胞维持在没有雄激素的培养基中，但是在包含雄激素的培养基中维持。在用对LNCaP细胞具有强大细胞毒性作用的肿瘤坏死因子-α预处理后，IM和TM均可诱导LNCaP细胞中GRP78转录的实质性增加，即使在含有雄激素的培养基中也是如此。在上述两种实验条件下，DNA片段化分析均显示IM处理后LNCaP细胞凋亡的发生与GRP78转录物诱导的开始之间存在直接相关性，而GRP78表达的诱导先于TM诱导的细胞凋亡。为了阐明IM和TM诱导GRP78的功能差异，设计了针对grp78基因的反义寡脱氧核苷酸（ODN），以序列特异性和剂量依赖性方式降低GRP78的表达。与错配对照ODN处理相比，反义GRP78 ODN处理显着增强了IM诱导的LNCaP细胞凋亡，而反义GRP78和错配对照ODN处理在TM诱导的凋亡特征中未观察到明显差异。对其他雄激素非依赖性前列腺癌PC3细胞的研究也表明，IM治疗后GRP78诱导与细胞凋亡抗性之间存在相关性，而TM治疗后则无相关性。这些发现表明至少有两个GRP78信号通路，它们在抵抗应激诱导的细胞凋亡中起着不同的作用。版权所有2000 Wiley-Liss，Inc.

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