Augmenter of liver regeneration (ALR) protects human hepatocytes against apoptosis.
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-β, 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-β 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.
Liver Regeneration Group, Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich, Germany.
Maren
M
Ilowski
Axel
A
Kleespies
Enrico N
EN
de Toni
Barbara
B
Donabauer
Karl-Walter
KW
Jauch
Jan G
JG
Hengstler
Wolfgang E
WE
Thasler
D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D003579:Cytochrome Reductases / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D019610:Cytoprotection; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008930:Mitochondria, Liver / Q000201:enzymology; D050862:Oxidoreductases Acting on Sulfur Group Donors
D045304:Cytochromes c; D003579:Cytochrome Reductases; C500897:GFER protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors