Augmenter of liver regeneration.
Augmenter of liver regeneration.
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DOI：
10.1186/1755-1536-5-10
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发表时间：
2012-07-09
期刊：
影响因子：
--
通讯作者：
Gandhi CR
中科院分区：
文献类型：
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作者：
Gandhi CR
“肝再生增强剂”（ALR）（也称为肝刺激物质或肝生成素）最初被发现可以促进再生或受损肝脏中肝细胞的生长。 ALR 在所有器官中普遍表达，并且仅在肝脏的肝细胞中表达。 ALR 是肝细胞的生存因子，与 ERV1（呼吸和活力所必需的）蛋白具有显着的同源性，而 ERV1 对酿酒酵母的生存至关重要。 ALR 包含 198 至 205 个氨基酸（约 22 kDa），但经过翻译后修饰为肝细胞中发现的三个高分子量种类（约 38 至 42 kDa）。 ALR 存在于线粒体、细胞质、内质网和细胞核中。线粒体ALR可能参与氧化磷酸化，但也起到巯基氧化酶和细胞色素c还原酶的作用，并导致蛋白质的Fe/S成熟。 ALR 由肝细胞分泌，通过 G 蛋白偶联受体刺激库普弗细胞中 TNF-α、IL-6 和一氧化氮的合成。虽然 22 kDa 的大鼠重组 ALR 不会刺激肝细胞中的 DNA 合成，但据报道，短形式 (15 kDa) 的人重组 ALR 作为肝细胞的有丝分裂原与 TGF-α 或 HGF 等效，甚至更强。某些病理状况下血清 ALR 水平的改变表明它可能是肝损伤/疾病的诊断标志物。尽管ALR似乎具有多种功能，但对其在包括肝脏在内的各种器官中的作用的了解极其不足，并且尚不清楚不同的ALR物种是否具有不同的功能。未来的研究应该可以更好地理解这种神秘分子的表达和功能。
‘Augmenter of liver regeneration’ (ALR) (also known as hepatic stimulatory substance or hepatopoietin) was originally found to promote growth of hepatocytes in the regenerating or injured liver. ALR is expressed ubiquitously in all organs, and exclusively in hepatocytes in the liver. ALR, a survival factor for hepatocytes, exhibits significant homology with ERV1 (essential for respiration and viability) protein that is essential for the survival of the yeast, Saccharomyces cerevisiae. ALR comprises 198 to 205 amino acids (approximately 22 kDa), but is post-translationally modified to three high molecular weight species (approximately 38 to 42 kDa) found in hepatocytes. ALR is present in mitochondria, cytosol, endoplasmic reticulum, and nucleus. Mitochondrial ALR may be involved in oxidative phosphorylation, but also functions as sulfhydryl oxidase and cytochrome c reductase, and causes Fe/S maturation of proteins. ALR, secreted by hepatocytes, stimulates synthesis of TNF-α, IL-6, and nitric oxide in Kupffer cells via a G-protein coupled receptor. While the 22 kDa rat recombinant ALR does not stimulate DNA synthesis in hepatocytes, the short form (15 kDa) of human recombinant ALR was reported to be equipotent as or even stronger than TGF-α or HGF as a mitogen for hepatocytes. Altered serum ALR levels in certain pathological conditions suggest that it may be a diagnostic marker for liver injury/disease. Although ALR appears to have multiple functions, the knowledge of its role in various organs, including the liver, is extremely inadequate, and it is not known whether different ALR species have distinct functions. Future research should provide better understanding of the expression and functions of this enigmatic molecule.