细胞外信号调节激酶在TPPB促进PC12产生可溶性淀粉样前体蛋白中的作用

Involvement of extracellular signal regulated kinase in the regulation of amyloid precursor protein processing in PC12 cells by TPPB

目的:观察在蛋白激酶C(PKC)激动剂TPPB促进可溶性淀粉样前体蛋白(sAPPα)释放过程中参与的信号转导通路。方法:以1μmol/L的TPPB作用于PC12细胞3h,同时加入信号转导通路的抑制剂,Western印迹法检测上清液内sAPPα的含量和细胞外信号调节激酶(p42/44MAPK)及磷酸化的p42/44MAPK的表达。结果:1μmol/L的TPPB作用于PC12细胞3h可以显著增加上清液内sAPPα的含量,细胞外信号调节激酶抑制剂U0126、c-Jun氨基末端激酶抑制剂SP600125和蛋白酪氨酸激酶抑制剂genistein可以部分消除此作用;而p38MAPK抑制剂SB203580对sAPPα的含量无显著影响。1μmol/L的TPPB可以使磷酸化的p42/44MAPK表达增加,而对总的p42/44MAPK无显著影响。结论:细胞外信号调节激酶、c-Jun氨基末端激酶和蛋白酪氨酸激酶可能参与TPPB促进sAPPα生成的过程。

AIM： To explore the signal transduction pathways involved in the regulation of amyloid precursor protein （APP） processing by protein kinase C （PKC） activator TPPB. METHODS： PC12 cells were treated with TPPB （ PKC activator） for 3 h and various signal transduction inhibitors were added to the conditioned medium to investigate their effects on α - secretase form of soluble amyloid precursor protein （sAPPα） secretion after TPPB treatment via Western blotting. Extracellular signal regulated kinase （ ERK, p42/44MAPK） and phospho - p42/44MAPK were also measured after TPPB treatment. RESULTS： TPPB （1μmol/L） significantly increased sAPPα secretion as compared with control group. The increase in sAPPα secretion by TPPB was partially blocked by ERK inhibitor U0126, c - Jun N - terminal kinase （JNK） inhibitor SP600125 and protein tyrosine kinase （PTK） inhibitor genistein, but not by p38MAPK inhibitor SB203580. TPPB （ 1μmol/L） increased the expression of phospho - p42/44MAPK without altering total p42/44MAPK levels. CONCLUSION： ERK, JNK and PTK may be involved in the regulation of APP processing by TPPB.