Augmenter of liver regeneration (ALR) protects human hepatocytes against apoptosis
Augmenter of liver regeneration (ALR) protects human hepatocytes against apoptosis
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DOI：
10.1016/j.bbrc.2010.11.083
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发表时间：
2011-01-07
影响因子：
3.1
通讯作者：
Thasler, Wolfgang E.
中科院分区：
文献类型：
--
作者：
Ilowski, Maren;Kleespies, Axel;Thasler, Wolfgang E.
已知肝再生增强因子（ALR）支持肝再生并刺激肝细胞增殖。然而，目前尚不清楚ALR是否在人肝细胞中发挥抗凋亡作用，以及这种保护作用是否具有细胞类型特异性。这是相关的，因为保护肝脏免于细胞凋亡而没有不期望的作用（例如保护转移性肿瘤细胞）的化合物将在几种临床环境中受到重视。将原代人肝细胞（phH）和器官型癌细胞系暴露于不同浓度的凋亡诱导剂（乙醇、TRAIL、抗Apo、TGF-β、放线菌素D），并与或不与重组人ALR（rhALR）一起培养。流式细胞仪检测线粒体细胞色素c的释放和碘化丙啶（PI）染色，ALR显著降低乙醇、TRAIL、抗Apo、TGF-β和放线菌素D诱导的细胞凋亡。此外，在原代人肝细胞和HepG 2细胞中观察到ALR的抗凋亡作用，但在支气管（BC 1）、结肠（SW 480）、胃（GC 1）和胰腺（L3.6PL）细胞系中未观察到ALR。与生长因子HGF和EGF不同，rhALR以肝脏特异性方式起作用。因此，ALR是一个有前途的候选人，进一步评估作为一个可能的肝保护因素在临床设置。(C)2010年爱思唯尔公司All rights reserved.
Augmenter of liver regeneration (ALR) is known to support liver regeneration and to stimulate proliferation of hepatocytes. However, it is not known if ALR exerts anti-apoptotic effects in human hepatocytes and whether this protective effect is cell type specific. This is relevant, because compounds that protect the liver against apoptosis without undesired effects, such as protection of metastatic tumour cells, would be appreciated in several clinical settings. Primary human hepatocytes (phH) and organotypic cancer cell lines were exposed to different concentrations of apoptosis inducers (ethanol, TRAIL, anti-Apo, TGF-beta, actinomycin D) and cultured with or without recombinant human ALR (rhALR). Apoptosis was evaluated by the release of cytochrome c from mitochondria and by FACS with propidium iodide (PI) staining.ALR significantly decreased apoptosis induced by ethanol, TRAIL, anti-Apo, TGF-beta and actinomycin D. Further, the anti-apoptotic effect of ALR was observed in primary human hepatocytes and in HepG2 cells but not in bronchial (BC1), colonic (SW480), gastric (GC1) and pancreatic (L3.6PL) cell lines.Therefore, the hepatotrophic growth factor ALR acts in a liver specific manner with regards to both its mitogenic and its anti-apoptotic effect. Unlike the growth factors HGF and EGF, rhALR acts in a liver specific manner. Therefore, ALR is a promising candidate for further evaluation as a possible hepatoprotective factor in clinical settings. (C) 2010 Elsevier Inc. All rights reserved.