Objective:To explore the effects of histone deacetylase 6(HDAC-6) on the PD cell model induced by proteasome inhibitor lactacystin.Methods:Human neuroblastoma SK-N-SH cells were cultured.The wild type pcDNA3.1-alpha-s...Objective:To explore the effects of histone deacetylase 6(HDAC-6) on the PD cell model induced by proteasome inhibitor lactacystin.Methods:Human neuroblastoma SK-N-SH cells were cultured.The wild type pcDNA3.1-alpha-synuclein eukaryotic expression plasmid was transferred into the cells which then were divided into control group,group L,group T and group T+L.The eells of group L were added with 5 umol/L lactacystin dissolved in dimethylsulfoxide(DMSO) to induce PD cell model with abnormal protein aggregation,the cells of control group were treated with 5 umol/L DMSO,the cells of group T were treated with 5 umol/L selective HDAC-6 inhibitor tubacin dissolved in DMSO,and the cells of group T+L were treated with 5 umol/L lactaeystin and 10 umol/L tubacin dissolved in DMSO.The expression levels of alpha-synuclein oligomers,HSP-27 and HSP-70 were detected by Western blot and the cell survival rate of all the groups was detected by MTT colorimetric assay,and compared 24 h after the cells were treated.Results:The expression levels of alpha-synuclein oligomers,HSP-27 and HSP-70 of the cells of group L were significantly higher than the control group,and the cell survival rate was significantly lower(P<0.05);the expression level of alpha-synuclein oligomers of the cells of group T+L was significantly higher than group L,but the expression level of HSP-27 and HSP-70 were significantly lower,and so as the cell survival rate(P<0.05);the differences of the expression level of alpha-synuclein oligomers,HSP-27 and HSP-70 and the cell survival rate of the cells of group T and the control group were not statistically significant(P>0.05).Conclusions:The expression level of alphasynuclein oligomers can be improved and the cell survival rate can be reduced by the PD cell model induced by lactacystin and treated with selective HDAC-6 inhibitor tubacin,which means that alpha-synuclein oligomers of the PD cell model induced by lactacystin can be inhibited and the cell survival rate can be improved by HDAC-6,and the mechanism may be related to the increased of HSP-27 and HSP-70.展开更多
基金supported by Natural Science Foundation of Guangdong Province:(gd28182334)
文摘Objective:To explore the effects of histone deacetylase 6(HDAC-6) on the PD cell model induced by proteasome inhibitor lactacystin.Methods:Human neuroblastoma SK-N-SH cells were cultured.The wild type pcDNA3.1-alpha-synuclein eukaryotic expression plasmid was transferred into the cells which then were divided into control group,group L,group T and group T+L.The eells of group L were added with 5 umol/L lactacystin dissolved in dimethylsulfoxide(DMSO) to induce PD cell model with abnormal protein aggregation,the cells of control group were treated with 5 umol/L DMSO,the cells of group T were treated with 5 umol/L selective HDAC-6 inhibitor tubacin dissolved in DMSO,and the cells of group T+L were treated with 5 umol/L lactaeystin and 10 umol/L tubacin dissolved in DMSO.The expression levels of alpha-synuclein oligomers,HSP-27 and HSP-70 were detected by Western blot and the cell survival rate of all the groups was detected by MTT colorimetric assay,and compared 24 h after the cells were treated.Results:The expression levels of alpha-synuclein oligomers,HSP-27 and HSP-70 of the cells of group L were significantly higher than the control group,and the cell survival rate was significantly lower(P<0.05);the expression level of alpha-synuclein oligomers of the cells of group T+L was significantly higher than group L,but the expression level of HSP-27 and HSP-70 were significantly lower,and so as the cell survival rate(P<0.05);the differences of the expression level of alpha-synuclein oligomers,HSP-27 and HSP-70 and the cell survival rate of the cells of group T and the control group were not statistically significant(P>0.05).Conclusions:The expression level of alphasynuclein oligomers can be improved and the cell survival rate can be reduced by the PD cell model induced by lactacystin and treated with selective HDAC-6 inhibitor tubacin,which means that alpha-synuclein oligomers of the PD cell model induced by lactacystin can be inhibited and the cell survival rate can be improved by HDAC-6,and the mechanism may be related to the increased of HSP-27 and HSP-70.
