The Effect And Mechanism Of HF On A? Production And Tau Phosphorylation In PC12 Cells Induced By Aluminum

Aluminum?Al?is a neurotoxicant,and excessive intake can cause nervous system dysfunction.Al can cause nerve damage via promoting the accumulation of?-amyloid?A??and tau hyperphosphorylation,which is the main pathomechanism of Alzheimer's disease?AD?.Hyperforin?HF?is one of the major active constituents of the extracts of Hypericum perforatum,can effectively relieve Alzheimer's disease?AD?and other cognition impairment induced by A?accumulation.To investigate the effects of HF on Al-malt-induced A?protein production,tau hyperphosphorylation and related mechanism,PC12 cells were cultured and divided into the control group?C?,Al-malt-treatment group?500?M Al-malt?,HF intervention group?500?M Al-malt+1?M HF?and HF-treatment group?1?M HF?.The viability of PC12 cells,the expressions of A?_1-42,APP,BACE1,PS1,ADAM9/10/17 and sAPP?,the protein expressions of phosphorylated tau?Ser396?and total tau,the protein expressions of phosphorylated GSK-3??Ser9?,GSK-3?,phosphorylated Akt?Ser473?and Akt were detected to investigate the effect of HF on A?protein production and tau phosphorylation in aluminum-induced PC12 cells and the regulation of Akt/GSK-3?signaling pathway.The results were shown as follows:1.The PC12 cells viability of Al-malt group was significantly lower than that of the control group?p<0.01?,while Al-malt+HF group was significantly higher than that of Al-malt group?p<0.01?,and there is no significant difference between the HF group and the control group,indicating that HF protects PC12 cells from Al-malt-induced cell damage,and HF alone has no toxic effect on PC12 cells.2.The expressions of APP,BACE1 and PS1 and A?_1-42 were significantly increased?p<0.05,p<0.01?,the expressions of ADAM9,ADAM10,ADAM17 and sAPP??p<0.01?were significantly decreased in Al-malt group as compared to the control group in PC12 cells,while the expressions of APP,BACE1 and PS1 and A?_1-42?p<0.01?were significantly decreased,the expressions of ADAM9,ADAM10,ADAM17 and sAPP??p<0.01?were significantly increased in Al-malt+HF group as compared to Al-malt group in PC12 cells,indicating that HF attenuates Al-malt-induced A?production by the inhibition of amyloidgenic pathway and enhancement non-amyloidgenic pathway.3.The ratio of pSer396-tau/total-tau was significantly increased in Al-malt group as compared to the control group?p<0.01?,while the ratio of pSer396-tau/total-tau was significantly decreased Al-malt+HF group as compared to the Al-malt group in PC12 cells?p<0.01?,indicating that HF attenuates tau hyperphosphorylation in Al-malt-induced PC12 cells.4.The ratios of pSer9-GSK-3?/GSK-3?and pSer473-Akt/Akt were significantly decreased in Al-malt group as compared to the control group?p<0.01?,while the ratios of pSer9-GSK-3?/GSK-3?and pSer473-Akt/Akt were significantly increased in Al-malt+HF group as compared to the Al-malt group in PC12 cells?p<0.01?,indicating that HF alleviates the down-regulation of Akt/GSK-3?signaling pathway in Al-malt-induced PC12 cells.Conclusion:HF can effectively alleviate aluminum-induced A?protein production and tau hyperphosphorylation in PC12 cells,and its mechanism is related to the activation of Akt/GSK-3?signaling pathway.The research results can provide theoretical basis and experimental basis for the amelioration of aluminum neurotoxicity.