title: Soluble asialoglycoprotein receptors reflect the apoptosis of hepatocytes.
abstract: Cell death is thought to take place through at least two distinct processes: apoptosis and necrosis. There is increasing evidence that dysregulation of the apoptotic program is involved in liver diseases. However, there is no method to simply evaluate apoptosis in the liver tissue at present. It has been reported that the expression of asialoglycoprotein receptors (AGPRs) increases with apoptosis, but there is no report until now that investigates the influence of soluble AGPRs on apoptosis of hepatocytes. Soluble AGPRs have been reported to be present in human serum under physiological conditions. In the present study, in order to investigate the correlation between apoptosis of hepatocytes and soluble AGPR, mouse soluble AGPRs were detected using SDS-PAGE and Western blot analysis was conducted using anti-extracellular mouse hepatic lectin-1 (Ex-MHL-1) antiserum (polyclonal rabbit serum). The mouse soluble AGPRs were present in culture medium and mouse serum when hepatocytes were damaged. The soluble AGPRs increased proportionately, as the number of dead hepatocytes increased. In addition, soluble AGPRs existed more when apoptotic cell death was observed in in vitro and in vivo than when necrotic cell death was observed. The extracellular moiety of MHL-1 exists in the culture medium and mouse serum as a soluble AGPR, but the detailed mechanism of releasing soluble AGPR from hepatocytes has not been revealed yet. We described the first evidence for the relation between quantity of soluble AGPRs with two kinds of cell death: necrosis and apoptosis. Based on the results of our study, soluble AGPRs might become a new marker of apoptosis in the liver tissue and be useful for clinical diagnosis and treatment for liver diseases.
authors.affiliation: Department of Organ Regeneration, Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Kakegawa
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Ise
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Sugihara
authors.forename: Toshio
authors.initials: T
authors.lastname: Nikaido
authors.forename: Naoki
authors.initials: N
authors.lastname: Negishi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akaike
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000502:physiology*; D037263:Asialoglycoprotein Receptor / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D001212:Asialoglycoproteins / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000032:analysis; D003470:Culture Media; D022781:Hepatocytes / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D009336:Necrosis; D019014:fas Receptor / Q000032:analysis
chemical_list: D000911:Antibodies, Monoclonal; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D003470:Culture Media; D019014:fas Receptor; D002251:Carbon Tetrachloride