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蛋白酶体抑制剂诱导的PC12细胞帕金森病模型中血红素加氧酶-1的差异表达
Differential Expression of Heme Oxygenase-1 in PC12 Cell Model of Parkinson Disease Induced by Proteasome Inhibitor
【摘要】 目的探讨蛋白酶体抑制剂(Proteasome inhibitor,PSI)诱导的PC12细胞帕金森病(Parkinson disease,PD)模型中血红素加氧酶-1(Hemeoxygenase-1,HO-1)的差异表达,为深入研究PD的发病机制提供理论依据。方法取培养的PC12细胞,加入终浓度为10μmol/L的PSI,建立PSI诱导的PC12细胞模型,以加入终浓度为10μmol/L的二甲基亚砜(DMSO)为对照组。经HE、AO&EB及α-SYN染色进行鉴定;PSI作用48h后提取蛋白,应用荧光差异凝胶电泳(DIGE)系统获得差异蛋白点,运用基质辅助激光解吸/电离飞行时间质谱仪(MALDI-TOFProMS)鉴定差异蛋白。结果模型组与对照组比较,PSI作用48h可见细胞内嗜酸性类Lewy小体形成及细胞凋亡,凋亡率达(24.74±4.55)%。模型组与对照组比较,HO-1表达量显著增加。结论在泛素-蛋白酶体系统(Ubiquitin-proteasome system,UPS)功能障碍诱发PD过程中,氧化应激反应发挥着一定的作用。
【Abstract】 Objective To investigate the differential expression of heme oxygenase-1(HO-1)in PC12 cell model of Parkinson disease (PD)induced by proteasome inhibitor (PSI)and provide theoretical basis for further study on pathogenic mechanism of PD. Methods PC12 cell model of PD was established by adding PSI to the cultured PC12 cells to a final concentration of 10 μmol / L, using the cells added with DMSO to a final concentration of 10 μmol / L as control, and identified by HE, AO & EB and α-SYN staining. Proteins were extracted from the PC12 cells 48 h after treatment with PSI to obtain differential protein spots by DIGE and identify differential proteins by MALDI-TOF-Pro MS. Results Acidophilic Lewy-like bodies were formed in the PC12 cells 48 h after treatment with PSI, and the apoptosis rate of cells reached(24. 74 ± 4. 55)%. The expression level of HO-1 in PC12 cells treated with PSI increased significantly as compared with those treated with DMSO. Conclusion Oxidative stress plays an important role in the pathogenesis of PD induced by functional disorder of ubiquitin-proteasome system(UPS).
【Key words】 Proteasome inhibitor(PSI); Heme oxygenase-1(HO-1); Ubiquitin; Peptide hydrolases; Parkinson disease(PD); PC12 cells;
- 【文献出处】 中国生物制品学杂志 ,Chinese Journal of Biologicals , 编辑部邮箱 ,2010年08期
- 【分类号】R742.5
- 【被引频次】3
- 【下载频次】160