title: [Oxidative stress promotes hepatocyte apoptosis mediated by glycogen synthase kinase 3β].
abstract: OBJECTIVE
  To analyze the role of glycogen synthase kinase 3β (GSK3β) in hepatocyte apoptosis induced by oxidative stress.
  
  
  METHODS
  Human HL-7702 hepatoma cells were induced by H₂O₂/antimycin A to establish oxidative stress-induced cell apoptosis models. SB216763, a specific inhibitor of GSK3β, was given to the cells two hours before H₂O₂/antimycin A induction. Cell survival was observed using calcein acetoxymethyl ester/propidium iodide (PI) double staining, and cell apoptosis was detected using annexin V-FITC/PI staining combined with flow cytometry. In the meanwhile, the cell culture supernatant was subjected to lactate dehydrogenase (LDH) assay to evaluate the extent of cell death. The expressions of p-GSK3β, GSK3β, caspase-3, cleaved caspase-3, c-Jun N-terminal kinase (JNK) and cytochrome C (CytC) proteins were examined using Western blotting.
  
  
  RESULTS
  Oxidative stress triggered by H₂O₂/antimycin A promoted GSK3β activity; inhibition of GSK3β activity by SB216763 relieved oxidative stress and reduced cell apoptosis induced by oxidative stress. Compared with the model groups, SB216763 intervened group showed that the cell apoptosis rate and the level of LDH were reduced significantly, and that the expressions of cleaved caspase-3, JNK, CytC proteins decreased.
  
  
  CONCLUSIONS
  GSK3β is an important signaling molecule in the apoptosis pathway induced by oxidative stress. The inhibition on GSK3β may alleviate the oxidative stress-induced hepatocyte apoptosis.
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing Institute of Hepatology, Beijing 100069, China.
authors.forename: Xiangying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing Institute of Hepatology, Beijing 100069, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing Institute of Hepatology, Beijing 100069, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing Institute of Hepatology, Beijing 100069, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wen
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing Institute of Hepatology, Beijing 100069, China.
authors.forename: Zhengfu
authors.initials: Z
authors.lastname: Piao
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing Institute of Hepatology, Beijing 100069, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Shi
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing Institute of Hepatology, Beijing 100069, China.
authors.forename: Dexi
authors.initials: D
authors.lastname: Chen
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing Institute of Hepatology, Beijing 100069, China.
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Duan
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing Institute of Hepatology, Beijing 100069, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ren
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D022781:Hepatocytes / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D006861:Hydrogen Peroxide; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D048031:JNK Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3