蛋白激酶C激动剂对可溶性淀粉样前体蛋白分泌的影响

Effects of Protein Kinase C Activator on Secretion of Soluble Amyloid Precursor Protein

目的 观察蛋白激酶C（PKC）激动剂（2S，5S）-（E，E）-8-（5-（4-（trifluoromethyl）phenyl）-2，4-pentadienoylamino）benzoctam（TPPB）在体外对淀粉样前体蛋白（APP）代谢的影响。方泼用不同浓度的TPPB作用于PCI2细胞3h，Western blot检测其对细胞培养上清液内可溶性淀粉样前体蛋白（sAPPα）分泌和细胞内APP表达的影响；并观察加入PKC抑制剂GF109203-X后TPPB对细胞外sAPPα分泌的影响。结果0．1～10μmoL／L的TPPB可以使sAPPα分泌增加，而对细胞本身APP的表达无显著影响（P〉0．05）；PKC抑制剂GF109203-X可以部分消除TPPB促进sAPPα分泌的作用。结论PKC激动剂TPPB可以使APP通过α分泌酶增加细胞对sAPPα的分泌，提示TPPB有可能对阿尔茨海默病具有潜在的治疗作用。

Objective To explore the effects of protein kinase C （PKC） activator （2S,5S）-（E,E）-8-（5-（4-（trifluoromethyl） phenyl）-2,4-pentadienoylamino） benzolactam （TPPB） on amyloid precursor protein （APP） processing in vitro. Methods PC12 cells were treated with different concentrations of TPPB for 3 h and Western blot was carried out to detect the secretion of α-secretase form of soluble amyloid precursor protein （sAPPa） in the supernatant and cellular full-length APP expression. In a separate group, PKC inhibitor GF109203-X was added to cell media to investigate its effect on sAPPα secretion after TPPB treatment. Results TPPB promoted sAPPα release as compared with control （ DMSO）, but did not significantly affected cellular APP expression （P 〉 0.05）. The effect of increasing sAPPα secretion by TPPB was partially blocked by PKC inhibitor GF109203-X. Conclusion TPPB can increase sAPPα secretion via α-secretase processing pathway and may have therapeutic potential in Alzheimer＇ s disease.