Molecular mechanisms of augmenter of liver regeneration as immunoregulator: its effect on interferon-γ expression in rat liver

African Swine Fever Virus pB119L Protein Is a Flavin Adenine Dinucleotide-Linked Sulfhydryl Oxidase

“…Concerning their biological effects, yeast Erv1p is essential for mitochondrial biogenesis, a function that can be complemented by the carboxy-terminal domain of human Alrp (4,22). It has also been demonstrated that mammalian Alrp has a regulatory role on mitochondrial gene expression and can also act as immunoregulator via its effect on gamma interferon expression (25,26). Furthermore, human hepatopoietin (HPO), as the Alrp protein is also designated, has been described as a hepatotrophic growth factor that binds to a specific cell surface receptor in hepatocytes and hepatoma cells and induces the stimulation of the mitogenactivated protein kinase cascade (20).…”

Expression of human augmenter of liver regeneration in pichia pastoris yeast and its bioactivity in vitro

“…These results suggested that ALR enhanced liver regeneration not only through indirect pathway i.e. immune regulation [1,[13][14][15][16] , but also through direct one. Our result showed that at the same concentration, hALR expressed in yeast had a stronger effect on the proliferation of HepG 2 and QGY than that expressed in E.coli, although it was reported that there was no N-glycosylation site in its amino acid sequence [1] .…”

Genetic Recombinant Expression and Characterization of Human Augmenter of Liver Regeneration

“…The inhibition of the liver-resident NK cells by ALR is achieved via reduction of IFNc by liver resident NK. The administration of IFNc in 70% hepatectomized rats is followed by a significant reduction both of the mitochondrial transcription factor A expression and of liver regeneration, indicating ALR as a growth factor and as an immunoregulator by controlling, through IFNc levels, the mitochondrial transcription factor A expression and the lytic activity of liver-resident NK cells [8,9,18,19]. Though ALR was first identified and cloned by Hagiya et al in 1994 [10], and since then more and more studies have focused on the distribution [3,4], functional identification [5,8,9], crystal structure analysis [6], as well as recombinant expression as mentioned above [12,[15][16][17], the low expression efficiency, incomplete characterization of recombinant human ALR (rhALR), and the extraordinary effect of rhALR on liver regeneration motivated us to establish a high effective expression system and then perform a serial of identification and functional studies so as to provide a solid basis for future clinical application of rhALR.…”

“…Thus, circulation of ALR is also regarded as the markers for liver cirrhosis and HCC [4]. Besides the effect as hepatocyte mitogen or potential marker for liver cirrhosis and HCC, ALR induces hepatocyte regeneration via inhibition of liver NK cells, since cytotoxicity of liver NK cells against regenerating hepatocytes has been reported as a possible mechanism of regeneration failure in fulminant hepatitis [8,9]. The inhibition of the liver-resident NK cells by ALR is achieved via reduction of IFNc by liver resident NK.…”

“…Recently, ALR was identified as a flavin-dependent sulfhydryl oxidase with cytochrome c reductase activity and immune regulator, belonging to the new Erv/Alr family [5][6][7]. It could control mitochondrial gene expression and the lytic activity of liver-resident natural killer (NK) cells through regulating interferon-c (IFNc) [8,9]. This secondary hepatotrophic protein, also known as hepatopoietin (HPO), can be obtained by gradient purification from hepatic stimulator substance (HSS) or genetic recombinant expression [10][11][12].…”