Red cell perturbations by amyloid β-protein
Red cell perturbations by amyloid β-protein
复制标题
DOI：
10.1016/s0304-4165(03)00101-6
复制
发表时间：
2003-06-20
影响因子：
3
通讯作者：
Rifkind, JM
中科院分区：
文献类型：
--
作者：
Jayakumar, R;Kusiak, JW;Rifkind, JM
淀粉样β蛋白（Amyloid beta-protein，Abeta）在脑内的蓄积被认为是导致阿尔茨海默病（Alzheimer's disease，AD）神经病理学的重要因素。Abeta与神经元和小胶质细胞的相互作用在AD中起关键作用。由于A β的血管沉积也与AD有关，因此红细胞与这些毒性聚集体的相互作用变得重要。然而，A与红细胞相互作用的影响还不太清楚。用生物素标记合成的淀粉样β蛋白（1-40），并在37 ℃下预孵育4、14和72小时以产生原纤维。流式细胞术用于研究这些纤维与红细胞的结合。淀粉样原纤维对红细胞具有高亲和力，对较长预孵育时间产生的较大原纤维具有更高的结合力。牛血清白蛋白（BSA）没有逆转结合，但实际上导致了Abeta原纤维与红细胞的更有效结合。Abeta与红细胞的相互作用增加了平均细胞体积，并导致细胞变得更加球形。这种影响是更大的较长的原纤维。与此同时，在37 ℃下孵育16小时后，Abeta与红细胞的相互作用使其荧光增强。这种荧光的增加归因于荧光血红素降解产物的形成。先前的血红蛋白氧化，过氧化氢酶抑制和谷胱甘肽过氧化物酶抑制的效果表明，淀粉样蛋白诱导的氧化损伤的红细胞涉及过氧化氢诱导的血红素降解。这些结果表明，淀粉样蛋白与红细胞的相互作用可能有助于AD的病理学。由爱思唯尔公司出版
Amyloid beta-protein (Abeta) accumulation in brain is thought to be important in causing the neuropathology of Alzheimer's disease (AD). Abeta interactions with both neurons and microglial cells play key roles in AD. Since vascular deposition of Abeta is also implicated in AD, the interaction of red cells with these toxic aggregates gains importance. However, the effects of A interactions with red blood cells are less well understood. Synthetic amyloid beta-protein (1-40) was labeled with biotin and preincubated at 37 degreesC for 4, 14 and 72 h to produce fibrils. Flow cytometry was used to study the binding of these fibrils to red cells. The amyloid fibrils had a high affinity for the red cell with increased binding for the larger fibrils produced by longer preincubation. Bovine serum albumin (BSA) did not reverse the binding, but actually resulted in a more efficient binding of the Abeta fibrils to the red cells. The interaction of Abeta with red cells increased the mean cell volume and caused the cells to become more spherical. This effect was greater for the longer fibrils. At the same time the interaction of Abeta with red cells produced an increase in their fluorescence measured after 16-h incubation at 37 degreesC. This increase in fluorescence is attributed to the formation of fluorescent heme degradation products. The effect of prior hemoglobin oxidation, catalase inhibition and glutathione peroxidase inhibition indicated that the amyloid-induced oxidative damage to the red cell involved hydrogen peroxide-induced heme degradation. These results suggest that amyloid interactions with the red cell may contribute to the pathology of AD. Published by Elsevier B.V.