title: Glycyrrhizin attenuates HMGB1-induced hepatocyte apoptosis by inhibiting the p38-dependent mitochondrial pathway.
abstract: OBJECTIVE
  To examine how high-mobility group box 1 (HMGB1) regulates hepatocyte apoptosis and, furthermore, to determine whether glycyrrhizin (GL), a known HMGB1 inhibitor, prevents HMGB1-induced hepatocyte apoptosis.
  
  
  METHODS
  A human hepatocellular carcinoma cell line stably transfected with a bile acid transporter (Huh-BAT cells), were used in this study. Apoptosis was quantified using 4',6-diamidino-2-phenylindole dihydrochloride staining and the APO Percentage apoptosis assay, and its signaling cascades were explored by immunoblot analysis. Kinase signaling was evaluated by immunoblotting and by using selective inhibitors. It is also tried to identify hepatocyte apoptosis affected by the HMGB1 inhibitor, GL.
  
  
  RESULTS
  HMGB1 increased cellular apoptosis in Huh-BAT cells. HMGB1 led to increased cytochrome c release from mitochondria into the cytosol, and induced the cleavage of procaspase 3. However, it did not affect the activation of caspase 8. HMGB1-induced caspase 3 activation was significantly attenuated by the p38 inhibitor SB203580. GL significantly attenuated HMGB1-induced hepatocyte apoptosis. GL also prevented HMGB1-induced cytochrome c release and p38 activation in Huh-BAT cells.
  
  
  CONCLUSIONS
  The present study demonstrated that HMGB1 promoted hepatocyte apoptosis through a p38-dependent mitochondrial pathway. In addition, GL had an anti-apoptotic effect on HMGB1-treated hepatocytes.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sugnkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-Gu, 135-710 Seoul, South Korea.
authors.forename: Geum-Youn
authors.initials: GY
authors.lastname: Gwak
authors.forename: Tae Gun
authors.initials: TG
authors.lastname: Moon
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Yoo
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D024243:HMGB1 Protein; D019695:Glycyrrhizic Acid; D048051:p38 Mitogen-Activated Protein Kinases