Expression of p53 during apoptosis induced by D-galactosamine and the protective role of PGE1 in cultured rat hepatocytes.
Expression of p53 during apoptosis induced by D-galactosamine and the protective role of PGE1 in cultured rat hepatocytes.
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DOI：
10.3923/pjbs.2011.976.983
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发表时间：
2011-11
期刊：
影响因子：
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通讯作者：
D. Fouad;F. Ataya;J. Muntané
中科院分区：
文献类型：
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作者：
D. Fouad;F. Ataya;J. Muntané
p53 在预防肿瘤发展中发挥着关键作用。它可以直接促进 DNA 修复和抑制血管生成，并随后诱导细胞凋亡。 p53 表达的调节由转录因子 NF-kappaB 介导。这包括 p53 蛋白稳定性的调节、其亚细胞定位的控制以及允许激活 p53 DNA 结合活性的构象变化。肝脏胶原酶灌注后从雄性 Wistar 大鼠中分离出大鼠肝细胞。我们通过蛋白质印迹法检测了肝细胞中 p53 表达水平的变化及其对 D-半乳糖胺、前列腺素 E1 和/或蛋白体抑制剂 (PSI) 治疗反应的细胞凋亡的影响。在肝细胞中进行了细胞外乳酸脱氢酶活性、NF-κB 激活、诱导一氧化氮合酶表达和一氧化氮产生的动力学研究。在对照和 D-半乳糖胺处理的肝细胞中添加前列腺素 E1 可以在 24 小时内增加细胞质中 p53 的表达。而在不存在前列腺素 E1 的情况下添加 PSI 会降低 5 mM D-半乳糖胺下的 p53 表达。当前列腺素 E1（5 和 40 mM D-半乳糖胺）存在时，这种抑制作用被逆转。前列腺素 E1 对 D-半乳糖胺的细胞凋亡作用的保护作用是通过 NF-kappaB 激活、诱导一氧化氮合酶和 p53 表达介导的。
p53 is a critical player in the prevention of tumor development. It can contribute directly to DNA repair and inhibition of angiogenesis and subsequently to the induction of apoptosis. The regulation of p53 expression is mediated by the transcription factor NF-kappaB. This includes regulation of p53 protein stability, control of its subcellular localization and conformational changes that allow activation of the DNA binding activity of p53. Rat hepatocytes were isolated from male Wistar rats following collagenase perfusion of liver. We examined the change in the expression level of p53 by western blotting in hepatocytes and its effect on apoptosis as a response of treatment with D-galactosamine, prostaglandin E1 and/or the Proteosome Inhibitor (PSI). A kinetic study of the extracellular lactate dehydrogenase activity, NF-kappaB activation, induced nitric oxide synthase expression and nitric oxide production was carried out in hepatocytes. The addition of prostaglandin E1 to control and D-galactosamine-treated hepatocytes increased p53 expression in the cytoplasm during 24 h. While the addition of PSI in the absence of prostaglandin E1 decreased p53 expression at 5 mM D-galactosamine. This inhibition is reversed in the presence of prostaglandin E1 at 5 and 40 mM D-galactosamine. The protective action of prostaglandin E1 against the apoptotic effect of D-galactosamine is mediated by NF-kappaB activation, induced nitric oxide synthase and p53 expression.