Lysosomal deposition of Aβ in cultures of brain vascular smooth muscle cells is enhanced by iron
Lysosomal deposition of Aβ in cultures of brain vascular smooth muscle cells is enhanced by iron
复制标题
DOI：
10.1016/j.brainres.2003.12.015
复制
发表时间：
2004-03-26
期刊：
影响因子：
2.9
通讯作者：
Mazur-Kolecka, B
中科院分区：
文献类型：
--
作者：
Frackowiak, J;Sukontasup, T;Mazur-Kolecka, B
最近，我们发现Tg2576小鼠的脑血管平滑肌细胞在培养中过度表达APP基因，分泌淀粉样β蛋白(Abeta)，并在细胞内积聚Abeta。现在我们在溶酶体内检测到这种细胞内的Abeta，它也富含APP的C-末端结构域，但不存在于内质网、高尔基体或TRAMS-高尔基网络中。用亚铁离子(50-150微米)处理培养的心肌细胞，细胞内Abeta1-40和Abeta1-42的含量及Abeta1-40和Abeta1-42的含量增加，并呈剂量依赖性。这种由铁引起的细胞内Abeta1-40的增加可以被α-生育酚抑制，但不能被水溶性抗氧化剂褪黑素所抑制。α-生育酚和褪黑素不能抑制铁引起的细胞内Abeta1-42的增加。用铁处理细胞不会改变Abeta免疫反应性的溶酶体定位。用铁(11和11)、铜(11)、锌(11)和铝(111)处理细胞可增加细胞内的羰基水平。然而，锌对培养物中Aβ的积累影响很小，铜和铝对此没有影响。这些数据表明，铁可能是引发血管淀粉样变性的因素。在Tg2576小鼠中，APP和Abeta的溶酶体积累启动了淀粉样蛋白在血管中的沉积。(C)2004爱思唯尔B.V.保留所有权利。
Recently, we found that brain vascular smooth muscle cells from Tg2576 mice over-expressed the APP transgene in culture, secreted amyloid-beta peptide (Abeta) and accumulated Abeta intracellularly. Now we detected this intracellular Abeta inside lysosomes, which were also rich in C-terminal domain of APP, but not in endoplasmic reticulum, Golgi apparatus, or trams-Golgi network. Treatment of cultures with ferrous ions (50-150 muM) increased the proportion of muscle cells with Abeta immunoreactive granules and the amounts of intracellular Abeta1-40 and Abeta1-42 in a dose-dependent manner. This increase of intracellular Abeta1-40 by iron was inhibited by alpha-tocopherol, but not by a water-soluble antioxidant melatonin. The increase of intracellular Abeta1-42 by iron was not inhibited by alpha-tocopherol or melatonin. Cell treatment with iron did not alter the lysosomal localization of Abeta immunoreactivity. Cell treatment with iron (11 and Ill), copper (11), zinc (11) and aluminum (111) increased cellular levels of carbonyls. However, the effect of zinc on Abeta accumulation in cultures was weak, and there were no effects of copper and aluminum. The data suggest that iron may be the factor that triggers vascular amyloidosis. Lysosomal accumulation of APP and Abeta initiates deposition of amyloid in blood vessels in Tg2576 mice. (C) 2004 Elsevier B.V. All rights reserved.