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. 2009 Jul 15;29(28):9078–9089. doi: 10.1523/JNEUROSCI.1071-09.2009

Figure 6.

Figure 6.

JNK inhibitor SP600125 blocked Aβ oligomer-induced aberrant inactivation of IRS-1 Ser616 and JNK-sensitive tau Ser422 phosphorylation in cultured hippocampal neurons. Hippocampal neurons were grown for 9 DIV and then pretreated with 10 μm JNK inhibitor, SP600125, for 30 min, followed by 100 nm Aβ42 oligomers for 5 h. After harvesting cells, pIRS-1 and ptau were evaluated by Western blot. A, B, Western immunoblot analysis of IRS-1 phosphorylation revealed induction by Aβ42 oligomers, which was antagonized by JNK inhibitor SP600125. pIRS-1 protein levels in membrane fractions were significantly increased by Aβ (B) (**p < 0.01), whereas JNK inhibitor SP600125 blocked the phosphorylated IRS-1 when compared with control (CTRL) (B) (**p < 0.01). A, C, Western immunoblot showed ptau was elevated by Aβ42 oligomers and JNK inhibitor SP600125 blocked this. ptau protein levels were significantly increased in cytosol (C) (***p = 0.001), whereas JNK inhibitor SP600125 significantly blocked the elevated ptau when compared with CTRL (C) (***p = 0.001). β-Actin was used for normalization. Error bars indicate SEM.