title: Tumor necrosis factor-alpha accelerates apoptosis of steatotic hepatocytes from a murine model of non-alcoholic fatty liver disease.
abstract: Non-alcoholic steatohepatitis (NASH) develops in a subset of patients with non-alcoholic fatty liver disease (NAFLD), but the exact mechanisms involved in the progression of NAFLD to NASH remain poorly understood. We investigated the role of tumor necrosis factor-alpha (TNF-alpha) in the apoptosis of hepatocytes that is related to the severity of NASH. We separated primary hepatocytes from the NAFLD liver caused by a high-fat diet. The production of intracellular reactive oxygen species was increased in steatotic hepatocytes, which were also sensitive to TNF-alpha. This factor induced significant apoptosis through the signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK) pathway. We describe here a novel culture model of steatotic hepatocytes separated from the NAFLD liver, and demonstrate that TNF-alpha induces their apoptosis in vitro.
authors.affiliation: Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kudo
authors.forename: Kengo
authors.initials: K
authors.lastname: Kawai
authors.forename: Shiho
authors.initials: S
authors.lastname: Fujisaka
authors.forename: Isao
authors.initials: I
authors.lastname: Usui
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukada
authors.forename: Naihong
authors.initials: N
authors.lastname: Chen
authors.forename: Terumi
authors.initials: T
authors.lastname: Takahara
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha