Regulation of polyamine synthesis in human hepatocytes by hepatotrophic factor augmenter of liver regeneration
Regulation of polyamine synthesis in human hepatocytes by hepatotrophic factor augmenter of liver regeneration
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DOI：
10.1016/j.bbrc.2006.04.040
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发表时间：
2006-06-23
影响因子：
3.1
通讯作者：
Weiss, Thomas S.
中科院分区：
文献类型：
--
作者：
Dayoub, Rania;Thasler, Wolfgang E.;Weiss, Thomas S.
肝再生的不同阶段受到多种因素的调控，如肝生长相关蛋白ALR，肝再生增强因子。此外，像多胺这样的小分子被证明是肝脏生长和再生所必需的。因此，在体外使用原代人肝细胞，我们研究了ALR对多胺生物合成的影响。我们通过HPLC分析证明，重组ALR在9-12小时内提高了细胞内肝腐胺、亚精胺和精胺水平。多胺生物合成的激活呈剂量依赖性，腐胺表现出最强的增加。此外，ALR处理诱导鸟氨酸脱羧酶（ODC）和S-腺苷甲硫氨酸脱羧酶，多胺生物合成的关键酶的mRNA表达。此外，ALR诱导c-myc mRNA表达。一种ODC表达的调节因子，因此我们假设ALR通过刺激其信号通路部分地导致增强的多胺合成来发挥其肝再生增强效应。(c)2006年爱思唯尔公司All rights reserved.
Different stages of liver regeneration are regulated by a variety of factors Such as the liver growth associated protein ALR, augmenter of liver regeneration. Furthermore, small molecules like polyamines were proven to be essential for hepatic growth and regeneration. Therefore, using primary human hepatocytes in vitro we investigated the effect of ALR on the biosynthesis of polyamines. We demonstrated by HPLC analysis that recombinant ALR enhanced intracellular hepatic putrescine, spermidine, and spermine levels within 9-12 h. The activation of polyamine biosynthesis was dose dependent with putrescine showing the strongest increase. Additionally, ALR treatment induced mRNA expression of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase, both key enzymes of polyamine biosynthesis. Further, ALR induced c-myc mRNA expression.. a regulator of ODC expression, and therefore we assume that ALR exerts its liver regeneration augmenting effects through stimulation of its signalling pathway leading in part to enhanced polyamine synthesis. (c) 2006 Elsevier Inc. All rights reserved.