烷丙苯胺对淀粉样前体蛋白代谢的影响

Effect of selegiline on amyloid precursor protein processing

目的利用人神经母细胞瘤SK-N-SH细胞和PC 12细胞观察烷丙苯胺对淀粉样前体蛋白(APP)代谢的影响。方法用不同浓度的烷丙苯胺分别作用于SK-N-SH和PC 12细胞2 h, Western印迹法检测细胞上清液内可溶性淀粉样前体蛋白(sAPPα)的分泌和细胞APP的表达,加入丝裂原激活的蛋白激酶和蛋白激酶C特异性抑制剂检测可能的信号转导通路。结果10μmol／L烷丙苯胺作用2 h能使SK-N-SH和PC 12细胞sAPPα的分泌显著增加,其灰度值分别为68．76±11．30和59．64±12．67,对照组分别为33．90±9．36和29．82±10．28,均为P<0．01;而对细胞本身APP的表达无影响,sAPPα的分泌增加能够被丝裂原激活的蛋白激酶和蛋白激酶C抑制剂所阻断。结论烷丙苯胺能通过α分泌酶代谢方向增加细胞sAPPα的分泌。

Objective To investigate the effect of seleginine on amyloid precursor protein （APP） processing. Methods Cells of SK-N-SH neuroblastoma and PC12 pheochromocytoma were treated with different concentrations of selegiline for 2 hours, soluble amyloid precursor protein a （sAPPa）secretion in the supernant and cellular APP expression were detected by Western blot. The mitogen-activated protein kinase （MAPK） and protien kinase C （PKC） inhibitors were added to cell media to explore the possible involved signal transduction pathways. Results sAPPa secretions in SK-N-SH and PC12 cells were significantly increased after 10 μmol/L seleginine treatment as compared with the normal control group（（68. 76±11.30）and（59.64±12.67） vs（33.90± 9.36）and （29.82± 10. 28）（P〈0.01）1, but cellular APP expression was not changed. The increased sAPPa secretion was blocked by MAPK inhibitor U0126 and PKC inhibitor staurosporine. Conclusions Selegiline can promote sAPPa secretion through a secretase processing pathway.