Gschwind M, Huber G
Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
J Neurochem. 1995 Jul;65(1):292-300. doi: 10.1046/j.1471-4159.1995.65010292.x.
beta-Amyloid peptide (A beta), a proteolytic fragment of the beta-amyloid precursor protein, is a major component of senile plaques in the brain of Alzheimer's disease patients. This neuropathological feature is accompanied by increased neuronal cell loss in the brain and there is evidence that A beta is directly neurotoxic. In the present study reduced cell viability in four different neuroblastoma cell types was observed after treatment with human A beta 1-42 for 1 day. Of the cell types tested rat PC12 and human IMR32 cells were most susceptible to A beta toxicity. Chromosomal condensation and fragmentation of nuclei were seen in PC12, NB2a, and B104 cells but not in IMR32 cells irrespective of their high sensitivity to A beta. Electrophoretic analysis of cellular DNA confirmed internucleosomal DNA fragmentation typical for apoptosis in all cell types except IMR32. These findings suggest that the form of A beta-induced cell death (necrosis or apoptosis) may depend on the cell type.
β-淀粉样肽（Aβ）是β-淀粉样前体蛋白的蛋白水解片段，是阿尔茨海默病患者大脑中老年斑的主要成分。这种神经病理学特征伴随着大脑中神经元细胞损失的增加，并且有证据表明Aβ具有直接神经毒性。在本研究中，用人类Aβ1-42处理1天后，观察到四种不同神经母细胞瘤细胞类型的细胞活力降低。在测试的细胞类型中，大鼠PC12细胞和人类IMR32细胞对Aβ毒性最敏感。在PC12、NB2a和B104细胞中可见细胞核的染色体浓缩和碎片化，但在IMR32细胞中未见，尽管它们对Aβ高度敏感。对细胞DNA的电泳分析证实，除IMR32外，所有细胞类型中均出现了典型的凋亡性核小体间DNA片段化。这些发现表明，Aβ诱导的细胞死亡形式（坏死或凋亡）可能取决于细胞类型。
