Department of Osteology, The Second Affiliated Hospital of Nantong University, Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, People's Republic of China.
Mol Cell Biochem. 2010 Jul;340(1-2):257-63. doi: 10.1007/s11010-010-0425-6. Epub 2010 Mar 16.
In Alzheimer's disease, beta-amyloid peptide (Abeta) could induce tau hyperphosphorylation which is the major cause of neuron apoptosis. However, the underlying mechanisms in the process remain unclear. In this study, Abeta-induced apoptosis and tau phosphorylation were investigated in differentiated PC12 cells. This Abeta-induced tau phosphorylation paralleled with the increase of expression and phosphorylation of Src-suppressed protein kinase C substrate (SSeCKS). By knocking down the expression of SSeCKS, Abeta-induced apoptosis and tau hyperphosphorylation in PC12 cells were partially rescued, and were increased further due to the overexpression of SSeCKS in PC12 cells. Also, the cell apoptosis and tau hyperphosphorylation were strongly decreased when the cells were pretreated with the protein kinase C inhibitor, Gö6983. In addition, Abeta-induced tau phosphorylation was also partially decreased due to the overexpression of SSeCKS in PC12cells. In summary, our data indicate that SSeCKS may play a critical role in Abeta-induced PC12 cells apoptosis through its phosphorylation.
在阿尔茨海默病中，β-淀粉样肽（Abeta）可诱导tau 过度磷酸化，这是神经元凋亡的主要原因。然而，这一过程中的潜在机制尚不清楚。在这项研究中，研究了 Abeta 在分化的 PC12 细胞中诱导的细胞凋亡和 tau 磷酸化。Abeta 诱导的 tau 磷酸化与 Src 抑制蛋白激酶 C 底物（SSeCKS）的表达和磷酸化增加平行。通过敲低 SSeCKS 的表达，Abeta 在 PC12 细胞中诱导的细胞凋亡和 tau 过度磷酸化部分得到挽救，并且由于 SSeCKS 在 PC12 细胞中的过表达而进一步增加。此外，当用蛋白激酶 C 抑制剂 Gö6983 预处理细胞时，细胞凋亡和 tau 过度磷酸化强烈减少。此外，由于 SSeCKS 在 PC12 细胞中的过表达，Abeta 诱导的 tau 磷酸化也部分减少。总之，我们的数据表明，SSeCKS 可能通过其磷酸化在 Abeta 诱导的 PC12 细胞凋亡中发挥关键作用。
