磷脂酰肌醇3-激酶/蛋白激酶B磷酸化是胰岛素受体后信号转导通路控制PC12细胞凋亡的机制

The Phosphorylation of Phosphatidylinositol 3'-OH Kinase/Protein Kinase B is an Effective Molecule in Insulin-Insulin Receptor Signal Transduction Against Apoptosis of PC12 Cells

目的:研究胰岛素抵抗1-甲基-4苯基砒啶(MPP+)诱导的PC12细胞凋亡的信号转导途径中,磷脂酰肌醇3-激酶/蛋白激酶B(PI3-K/PKB)的活力变化。方法:应用Wortmannin(PI3-K抑制剂),比较用药前后细胞生存率的变化;应用Western印迹分析检测此间PKB及其磷酸化水平的变化。结果:Wortmannin预处理组细胞生存率较之胰岛素干预组明显下降;PKB的特异性磷酸化程度(Ser473磷酸化程度/激酶蛋白量)与细胞生存率的变化有关。结论:胰岛素主要通过调节PI3-K活性后再促进PKB的磷酸化,从而促进PKB的激活,并导致生物学效应的变化,但是尚不能排除其他机制的参与。

Aim. To study the effect of PI3-K/PKB in the pathway of insulin-insulin receptor signal transduction against apoptosis of PC 12 cells. Methods： With Wortmannin the specific inhibitor of PI3-K, compared the change of the PC 12 cells viability; with Western immunoblotting method, analysed the change of the phosphorylation of PKB. Results： Cell treated with Wortmannin exhibited lower cells viability than insulin-treated. The phosphorylation of PKB at Serine（Ser）473 residues altered in different experiment conditions accordingly. Conclusion. The phosphorylation of PKB was an important molecule against MPP^＋-induced apoptosis in PC 12 cells