Insights on augmenter of liver regeneration cloning and function

Abstract

Hepatic stimulator substance (HSS) has been referred to as a liver-specific but species non-specific growth factor. Gradient purification and sequence analysis of HSS protein indicated that it contained the augmenter of liver regeneration (ALR), also known as hepatopoietin (HPO). ALR, acting as a hepatotrophic growth factor, specifically stimulated proliferation of cultured hepatocytes as well as hepatoma cells in vitro, promoted liver regeneration and recovery of damaged hepatocytes and rescued acute hepatic failure in vivo. ALR belongs to the new Erv1/Alr protein family, members of which are found in lower and higher eukaryotes from yeast to man and even in some double-stranded DNA viruses. The present review article focuses on the molecular biology of ALR, examining the ALR gene and its expression from yeast to man and the biological function of ALR protein. ALR protein seems to be non-liver-specific as was previously believed, increasing the necessity to extend research on mammalian ALR protein in different tissues, organs and developmental stages in conditions of normal and abnormal cellular growth.

Liver Regeneration Associated Protein (ALR) Exhibits Antimetastatic Potential in Hepatocellular Carcinoma

“…The short form of ALR (15 kDa) is found not only at extracellular sites but also at nuclear and cytosolic localizations participating in intracellular redox-dependent signaling pathways (15,16). ALR is a hepatotrophic factor stimulating proliferation of hepatocytes (17,18) and augmenting liver regeneration (15,16), thereby exerting beneficial effects in models of hepatic failure (19) and liver fibrosis (20).…”

Molecular recognition and substrate mimicry drive the electron-transfer process between MIA40 and ALR

“…Its activity is essential for the survival of the cell, for the biogenesis of mitochondria and for the maturation of cytoplasmic proteins with mitochondrially assembled iron-sulfur clusters (4)(5)(6)(7). ALR is found in two main alternatively spliced forms (8). The long form of the oxidase (lf-ALR, 23 kDa) exists predominantly in the mitochondrial intermembrane space (IMS) and contains an 80-amino acid N-terminal extension with respect to the short form (sf-ALR, 15 kDa) (9) (Fig.…”

Glycochenodeoxycholate-Induced Apoptosis Is Not Reduced by Augmenter of Liver Regeneration in the Human Hepatoma Cell Line HuH-7

“…Moreover, after partial hepatectomy, an increase of serum but not of liver ALR levels was observed in rats [5] , and increased expression of ALR mRNA was observed in cirrhotic human livers [6] . ALR is a homolog of the Erv1 protein from yeast that is essential for mitochondrial respiration and cell viability [7] , and is a member of the Erv1/ALR protein family of sulfhydryl oxidases [8][9][10] . This protein family is important for mitochondrial biogenesis, cell cycle, and hepatic and testicular organogenesis [10] .…”

“…ALR is a homolog of the Erv1 protein from yeast that is essential for mitochondrial respiration and cell viability [7] , and is a member of the Erv1/ALR protein family of sulfhydryl oxidases [8][9][10] . This protein family is important for mitochondrial biogenesis, cell cycle, and hepatic and testicular organogenesis [10] . Previous studies in rat hepatocytes and human HepG2 hepatoma cells described FuGene transfection reagent (Roche, Mannheim, Germany), similar as described previously [21] .…”