title: [Involvement of Toll-like receptor 4 in apoptosis of hippocampal neurons through Akt/FoxO3a/Bim signaling pathways].
abstract: The present study was to investigate whether Toll-like receptor 4 (TLR4)-mediated Akt/FoxO3a/Bim signaling pathway participated in lipopolysaccharide (LPS)-induced apoptosis in hippocampal neurons. The primarily cultured rat hippocampal neurons were treated with LPS, TLR4 antibody+LPS, and LY294002+LPS, respectively. Cell vitality was assayed by CCK-8. Expressions of p-Akt, Akt, p-FoxO3a, FoxO3a, Bim and active-Caspase-3 of each group were detected by Western blot analysis; the mRNA expression of Bim was detected by real-time quantitative PCR; FoxO3a nuclear translocation was detected by fluorescence microscope. The rate of cell apoptosis was assayed by flow cytometry. The results showed that cell vitality of hippocampal neurons decreased after being treated with LPS in a time-dependent way. Compared with the control group, the expressions of p-Akt and p-FoxO3a decreased significantly, FoxO3a translocated into the nucleus, meanwhile, the expression of Bim and active-Caspase-3, and the apoptotic ratio of hippocampal neurons increased in LPS treated neurons. Pretreatment with TLR4 antibody significantly blocked, while PI3K antagonist LY294002 further strengthened these changes induced by LPS. In conclusion, the present study suggests that Akt/FoxO3a/Bim signaling pathways mediated by TLR4 participate in the apoptotic processes of primarily cultured hippocampal neurons treated with LPS, and the activation of TLR4 causes neuronal apoptosis.
authors: Department of Pathophysiology, Medical College of Nantong University; Department of Neurology, Affiliated Hospital of Nantong University, Nantong 226001, China. alz@ntu.edu.cn.
authors: Ling
authors: L
authors: Xu
authors: Ai-Ling
authors: AL
authors: Zhou
authors: Min
authors: M
authors: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D053148:Caspase 3 / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D008070:Lipopolysaccharides; D008565:Membrane Proteins / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606778:Bcl2l11 protein, rat; D002867:Chromones; C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; C505410:Casp3 protein, rat; D053148:Caspase 3