Yamamori Hidenaga, Tanaka Toshihisa, Kudo Takashi, Takeda Masatoshi
Division of Psychiatry and Behavioral Proteomics, Department of Post-Genomics and Diseases, Course of Advanced Medicine, Osaka University, Graduate School of Medicine. D-3, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Neuroreport. 2004 Apr 9;15(5):851-4. doi: 10.1097/00001756-200404090-00023.
Recent observations suggest that amyloid-beta (Abeta), a major constituent of senile plaques, induces apoptosis in cultured neuronal cells. However, the concentration of Abeta that leads to neuronal cell death is much higher (10-25 microM) than that in the cerebrospinal fluid of normal controls or AD patients (nM order). As reported here, we found that subtoxic concentrations (100-500 nM) of Abeta(1-42) can down-regulate the expression of the X-linked inhibitor of apoptosis (XIAP) in human SH-SY5Y neuroblastoma cells, and that vulnerability to oxidative stress caused by Abeta(1-42) is attenuated by over-expression of XIAP. These results suggest that down-regulation of XIAP expression in response to subtoxic, more physiological concentrations (100-500 nM) of Abeta(1-42) increases vulnerability to oxidative stress.
最近的观察结果表明，老年斑的主要成分β淀粉样蛋白（Aβ）可诱导培养的神经元细胞凋亡。然而，导致神经元细胞死亡的Aβ浓度（10 - 25微摩尔）远高于正常对照或阿尔茨海默病患者脑脊液中的浓度（纳摩尔水平）。如本文所报道，我们发现亚毒性浓度（100 - 500纳摩尔）的Aβ（1 - 42）可下调人SH - SY5Y神经母细胞瘤细胞中X连锁凋亡抑制蛋白（XIAP）的表达，并且XIAP的过表达可减轻由Aβ（1 - 42）引起的氧化应激易感性。这些结果表明，对亚毒性、更接近生理浓度（100 - 500纳摩尔）的Aβ（1 - 42）作出反应时，XIAP表达的下调会增加氧化应激易感性。
