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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

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【作者】 杨红旗陈生弟巴茂文任汝静张宇红谭玉燕陆国强

【Author】 YANG Hong-qi, CHEN Sheng-di, BA Mao-wen, REN Ru-jing, ZHANG Yu-hong, TAN Yu-yan, LU Guo-qiang. Department of Neurology and Institute of Neurology, Ruijin Hospital, Medical School of Shanghai Jiaotong University, Shanghai 200025 , China

【摘要】 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。

【Abstract】 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 proteinα(sAPPα)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 sAPPαsecretions in SK-N-SH and PC12 cells were significantly increased after 10βmol/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) (F<0. 01)3, but cellular APP expression was not changed. The increased sAPPαsecretion was blocked by MAPK inhibitor U0126 and PKC inhibitor staurosporine. Conclusions Selegiline can promote sAPPαsecretion through a secretase processing pathway.

【基金】 国家重点基础研究发展计划(973计划)项目(2006CB500706)
  • 【文献出处】 中华老年医学杂志 ,Chinese Journal of Geriatrics , 编辑部邮箱 ,2006年08期
  • 【分类号】R749.161
  • 【下载频次】73
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