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Yang B.-Z.,Shanxi Medical University | Ren F.,Institute of Liver Disease | Wen T.,Institute of Liver Disease | Yin J.-M.,Institute of Liver Disease | And 8 more authors.
World Chinese Journal of Digestology | Year: 2012

AIM: To study the role of glycogen synthase kinase-3β (GSK-3β) in the pathogenesis of acute liver failure (ALF) induced by injection of D-galactosamine/ lipopolysaccharide (D-GalN/LPS) in mice. METHODS: ALF was induced in C57BL/6 mice by intraperitoneal injection of D-GalN/LPS. Animal experimental groups included control group, ALF model group, SB216763 pretreatment group (SB216763 in DMSO, i.p, two hours before the induction of ALF) and SB216763 treatment group (SB216763 in DMSO, i.p, two hours after the induction of ALF). Phosphorylation level of GSK- 3β was analyzed by Western blot. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured to assess the liver function. HE staining was conducted to analyze histological injury. Inflammatory gene expression was detected by quantitative real-time PCR. The expression of apoptosis-related protein Caspase 3 was detected by Western blot. Oneway ANOVA was used for pair-wise comparison of means of multiple samples (homogeneity of variance with LSD-t test, unequal variances with Games-Howell method). RESULTS: The phosphorylation level of GSK- 3β decreased initially and then increased in the progression of ALF. Inhibition of GSK-3β, either by pretreatment or treatment with SB216763, could improve liver function (serum ALT and AST levels decreased significantly, and there was obvious improvement in liver tissue injury), suppress inflammatory responses (inhibition of expression of pro-inflammatory cytokines, such as TNF-α, IL-6 and IL-1β, and promotion of expression of anti-inflammatory cytokine IL-10), and reduced the expression of apoptosis-related protein Caspase 3. CONCLUSION: GSK-3β is activated in D-GalN/ LPS-induced ALF in mice, and inhibition of GSK-3β activity can improve liver injury by reducing inflammation and hepatocyte apoptosis, GSK-3β may be a new target for the treatment of ALF. © 2012, WJC Press. All rights reserved.

Ding S.,Ningbo University | Hu A.,Ningbo University | Hu A.,Institute of Liver Disease | Hu Y.,Ningbo University | And 4 more authors.
Tumor Biology | Year: 2014

The aim of this study is to explore the apoptotic induction and cell cycle arrest function of luteolin on the liver cancer cells and the related mechanism. The liver cancer cell line SMMC-7721, BEL-7402, and normal liver cells HL-7702 were treated with different concentrations of luteolin. Cell proliferation ability was tested. Morphological changes of the apoptotic cells were observed under inverted fluorescence microscope after Hoechst33342 staining. We investigated the effect of luteolin on cell cycling and apoptosis with flow cytometry. The mitochondrial membrane potential changes were analyzed after JC-1 staining. Caspases-3 and Bcl-2 family proteins expression were analyzed by real-time PCR. Cell proliferation of SMMC-7721 and BEL-7402 were inhibited by luteolin, and the inhibition was dose-time-dependent. Luteolin could arrest the cells at G1/S stage, reduce mitochondrial membrane potential, and induce higher apoptosis rate and the typical apoptotic morphological changes of the liver carcinoma cells. Q-RT-PCR results also showed that luteolin increased Bax and caspase-3 expression significantly and upregulated Bcl-2 expression in a dose-dependent manner in liver carcinoma cells. However, the normal liver cells HL-7702 was almost not affected by luteolin treatment. Luteolin can inhibit SMMC-7721 and BEL-7402 cell proliferation in a time- and dose-dependent manner. And the mechanism maybe through arresting cell cycle at phase G1/S, enhancing Bax level, reducing anti-apoptotic protein Bcl-2 level, resulting in activating caspase-3 enzyme and decrease of mitochondrial membrane potential, and finally leading to cell apoptosis. © 2013 International Society of Oncology and BioMarkers (ISOBM).

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