title: Programmed hepatocytes cell death associated with FLIP downregulation in response to extracellular preS1/2.
abstract: Chronic hepatitis B virus (HBV) infection involves liver damage resulting in continuous cell injury and death. During HBV infection, hepatocytes exhibit changes in death receptor expression and in their susceptibility to death. These changes are observed not only in infected cells but also in bystander cells. Because excess viral surface protein (HBsAg) is secreted in large amounts as soluble particles containing preS proteins, the role of soluble preS1/2 in hepatocyte (HepG2) death modulation is an important issue to be explored. An increase of cell death induced by preS1/2 was observed. Also, cell death was associated with the down-regulation of FLIP and activation of caspase 8, caspase 9, and BID. Additionally, hepatocytes exhibited a sensitization to death mediated by the Fas receptor. These results, may contribute to understanding the role of envelope proteins (preS1/2) in the pathogenesis of HBV infection.
authors.affiliation: Instituto de Inmunología Clínica, Universidad de Los Andes, Merida, Venezuela.
authors.forename: Masyelly D
authors.initials: MD
authors.lastname: Rojas
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Peterson
authors.forename: Luisa
authors.initials: L
authors.lastname: Barboza
authors.forename: Guillermo
authors.initials: G
authors.lastname: Terán-Ángel
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Labastida-Moreno
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Berrueta
authors.forename: Siham
authors.initials: S
authors.lastname: Salmen
mesh_terms: D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D015536:Down-Regulation; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000378:metabolism*; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000502:physiology* / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D006514:Hepatitis B Surface Antigens; C505530:CASP8 protein, human; D053181:Caspase 8; D053453:Caspase 9
keywords: BID; FLIP; Fas/FasL; HepG2; caspase 8; caspase 9; hepatocytes; preS1/2