Institute for Biomedical Research, Kaunas University of Medicine, Kaunas, Lithuania; Department of Biochemistry, Kaunas University of Medicine, Kaunas, Lithuania.
Arch Biochem Biophys. 2010 Apr 15;496(2):84-92. doi: 10.1016/j.abb.2010.02.001. Epub 2010 Feb 11.
The link between the size of soluble amyloid beta (Abeta) oligomers and their toxicity to rat cerebellar granule cells (CGC) was investigated. Variation in conditions during in vitro oligomerization of Abeta(1-42) resulted in peptide assemblies with different particle size as measured by atomic force microscopy and confirmed by dynamic light scattering and fluorescence correlation spectroscopy. Small oligomers of Abeta(1-42) with a mean particle z-height of 1-2 nm exhibited propensity to bind to phospholipid vesicles and they were the most toxic species that induced rapid neuronal necrosis at submicromolar concentrations whereas the bigger aggregates (z-height above 4-5 nm) did not bind vesicles and did not cause detectable neuronal death. A similar neurotoxic pattern was also observed in primary cultures of cortex neurons whereas Abeta(1-42) oligomers, monomers and fibrils were non-toxic to glial cells in CGC cultures or macrophage J774 cells. However, both oligomeric forms of Abeta(1-42) induced reduction of neuronal cell densities in the CGC cultures.
研究了可溶性淀粉样β（Abeta）寡聚物的大小与其对大鼠小脑颗粒细胞（CGC）的毒性之间的关系。通过原子力显微镜测量和动态光散射以及荧光相关光谱证实，Abeta（1-42）在体外寡聚化过程中条件的变化导致肽组装具有不同的颗粒大小。平均颗粒 z 高度为 1-2nm 的 Abeta（1-42）小寡聚物表现出与磷脂囊泡结合的倾向，并且它们是最具毒性的物种，在亚毫摩尔浓度下诱导快速神经元坏死，而较大的聚集物（z 高度高于 4-5nm）则不与囊泡结合，也不会引起可检测到的神经元死亡。在皮质神经元的原代培养中也观察到类似的神经毒性模式，而 Abeta（1-42）寡聚物、单体和纤维对 CGC 培养物中的神经胶质细胞或巨噬细胞 J774 细胞没有毒性。然而，Abeta（1-42）的两种寡聚物形式都导致 CGC 培养物中神经元细胞密度降低。
