Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2015, Article ID 631326, 11 pages
Research Article

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

1Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China
2Department of Infectious Disease, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China
3Department of Science Technology and Industry, Nantong University, Nantong, Jiangsu 226019, China
4Department of Pathophysiology, Nantong University, Nantong, Jiangsu 226001, China

Received 16 September 2015; Revised 9 November 2015; Accepted 17 November 2015

Academic Editor: Antoni Camins

Copyright © 2015 Xian Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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-, P-GSK-, 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- and P-GSK- 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- further decreased following pretreatment with LY294002 and the expression of P-GSK- increased following pretreatment with LiCl. Moreover, pretreatment with CLI-095 weakened LPS-induced nuclear translocation of GSK-3β. Our findings suggest that the TLR4-mediated PI3K/AKT/GSK-3β signaling pathway is present in rat hepatocytes and participates in apoptosis of BRL-3A cells.