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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Inhibition of tumor necrosis factor-induced necrotic cell death by the zinc finger protein A20.
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Inhibition of tumor necrosis factor-induced necrotic cell death by the zinc finger protein A20.

机译：锌指蛋白A20抑制肿瘤坏死因子诱导的坏死细胞死亡。

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摘要

Tumor Necrosis Factor (TNF) is a cytokine that induces necrotic and apoptotic forms of cell death. The TNF-induced signalling mechanisms leading to necrosis or apoptosis are partially distinct, and are therefore likely to be regulated in a different way. The zinc finger protein A20 is a TNF-induced primary response gene that has been shown to inhibit TNF-induced apoptosis. However, its ability to inhibit the necrotic route of cell death as well as the underlying mechanism remains unknown. Here we show that stable expression of A20 or a fusion protein consisting of Green Fluorescent Protein (GFP) and A20 protects the TNF-sensitive fibroblast cell line L929 partially from TNF-induced necrotic cell death. TNF-induced necrosis has been shown to involve the activation of several phospholipases, as well as an increased production of reactive oxygen radicals. The reduced TNF-sensitivity of A20-expressing L929 cells was correlated with a decrease of TNF-induced phospholipase A2 (PLA2), phospholipase C (PLC) and phospholipase D (PLD) activation. Furthermore, production of mitochondrial reactive oxygen intermediates was retarded by overexpression of A20. These results demonstrate that A20 not only inhibits TNF-induced apoptosis but also TNF-induced necrosis, suggesting that it interferes with an early step in TNF signalling which is required for both types of cell death.
机译：肿瘤坏死因子（TNF）是诱导坏死和凋亡形式细胞死亡的细胞因子。 TNF诱导的导致坏死或凋亡的信号传导机制部分不同，因此可能以不同的方式进行调节。锌指蛋白A20是TNF诱导的主要反应基因，已显示抑制TNF诱导的细胞凋亡。然而，其抑制细胞死亡的坏死途径的能力以及潜在机制仍然未知。在这里，我们显示A20或由绿色荧光蛋白（GFP）和A20组成的融合蛋白的稳定表达可保护TNF敏感的成纤维细胞L929部分免受TNF诱导的坏死细胞死亡。 TNF诱导的坏死已显示涉及几种磷脂酶的活化，以及增加的活性氧自由基的产生。表达A20的L929细胞的TNF敏感性降低与TNF诱导的磷脂酶A2（PLA2），磷脂酶C（PLC）和磷脂酶D（PLD）活化的降低有关。此外，线粒体活性氧中间体的生产因A20的过表达而受阻。这些结果表明，A20不仅抑制TNF诱导的细胞凋亡，而且抑制TNF诱导的坏死，表明它干扰了两种细胞死亡所必需的TNF信号传导的早期步骤。

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