Role of TLR4-Mediated PI3K/AKT/GSK-3β Signaling Pathway in Apoptosis of Rat Hepatocytes

BioMed Research International
Xian ZhangJianhe Gan

Abstract

We investigated the mechanism of the Toll-like receptor 4- (TLR4-) mediated PI3K/AKT/GSK-3β signaling pathway in rat hepatocytes apoptosis induced by LPS. The cultured rat hepatocytes were treated with LPS alone or first pretreated with TLR4 inhibitor, AKT inhibitor, and GSK-3β inhibitor, respectively, and then stimulated with the same dose of LPS. Cell viability, cell apoptotic rate, and apoptosis morphology were assessed; the level of P-AKT(Ser473), P-GSK-3β(Ser9), and active Caspase-3 and the ratio of Bax/Bcl-2 were evaluated. The results indicated that cell viability decreased, while cell apoptotic rate increased with time after LPS stimulation. The expression of P-AKT(Ser473) and P-GSK-3β(Ser9) in the LPS group decreased compared with the control, while the level of active Caspase-3 and the ratio of Bax/Bcl-2 were significantly increased. These effects were attenuated by pretreatment with CLI-095. In addition, the apoptotic ratio decreased after pretreatment with LiCl but increased following pretreatment with LY294002. The expression of P-AKT(Ser473) further decreased following pretreatment with LY294002 and the expression of P-GSK-3β(Ser9) increased following pretreatment with LiCl. Moreover, pretreatment with CLI-095 wea...Continue Reading

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Citations

Mar 4, 2018·Cell Death & Disease·Agustina NoaillesNicolás Cuenca
Apr 14, 2020·Journal of Biochemical and Molecular Toxicology·Ling WangWei Wang
Jun 15, 2019·Histochemistry and Cell Biology·Dongmei SuYunjun Zhou
May 8, 2020·Brain Research Bulletin·Yajie ChiXiaobing Xu
Apr 1, 2020·Current Stem Cell Research & Therapy·Haiping LiuXiaodong Wang
Jul 29, 2021·Journal of Microbiology and Biotechnology·Woodvine OtienoYanhong Ji

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Methods Mentioned

BETA
Flow Cytometric
flow cytometry
Assay
PCR
nuclear translocation

Software Mentioned

SPSS

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