Selenoprotein P and apolipoprotein E receptor-2 interact at the blood-brain barrier and also within the brain to maintain an essential selenium pool that protects against neurodegeneration
Selenoprotein P and apolipoprotein E receptor-2 interact at the blood-brain barrier and also within the brain to maintain an essential selenium pool that protects against neurodegeneration
复制标题
DOI：
10.1096/fj.14-252874
复制
发表时间：
2014-08-01
期刊：
影响因子：
4.8
通讯作者：
Zhang, Wanqi
中科院分区：
文献类型：
--
作者：
Burk, Raymond F.;Hill, Kristina E.;Zhang, Wanqi
硒蛋白P(Sepp1)及其受体载脂蛋白E受体2(ApoER2)比其他组织更好地解释了大脑对硒的保留。Sepp1在血浆和脑中的主要来源分别是肝细胞和星形胶质细胞。ApoER2在组织中以不同的数量表达；在大脑中，它主要由神经元表达。Sepp1或ApoER2基因敲除后，大脑的硒含量从接近120 ng/g降至接近50 ng/g，在轻度缺硒的情况下会导致严重的神经变性和死亡。Sepp1和ApoER2之间的相互作用对这种损伤的保护作用尚未确定。我们在基因敲除小鼠中研究了Sepp1、ApoER2和脑硒。免疫细胞化学显示ApoER2介导血脑屏障对Sepp1的摄取。当Sepp1(-/-)或ApoER2(-/-)小鼠出现轻度缺硒引起的严重神经变性时，脑硒接近35 ng/g。然而，在极度缺硒时，当Sepp1和ApoER2在大脑中都完整时，脑硒可耐受类似于12 ng/g的脑硒。这些发现表明，Sepp1-ApoER2串联相互作用为脑神经元的维持提供了硒。一种相互作用发生在血脑屏障上，另一种发生在大脑内部。我们假设血脑屏障内的Sepp1被神经元通过ApoER2摄取，并在其中浓缩脑硒。-Burk，R.F.，Hill，K.E.，Motley，A.K.，Winfrey，V.P.，Kurokawa，S.，Mitchell，S.L.，Zhang，W.硒蛋白P和载脂蛋白E受体-2在血脑屏障和脑内相互作用，以维持防止神经退化的必要硒池。
Selenoprotein P (Sepp1) and its receptor, apolipoprotein E receptor 2 (apoER2), account for brain retaining selenium better than other tissues. The primary sources of Sepp1 in plasma and brain are hepatocytes and astrocytes, respectively. ApoER2 is expressed in varying amounts by tissues; within the brain it is expressed primarily by neurons. Knockout of Sepp1 or apoER2 lowers brain selenium from similar to 120 to similar to 50 ng/g and leads to severe neurodegeneration and death in mild selenium deficiency. Interactions of Sepp1 and apoER2 that protect against this injury have not been characterized. We studied Sepp1, apoER2, and brain selenium in knockout mice. Immunocytochemistry showed that apoER2 mediates Sepp1 uptake at the blood-brain barrier. When Sepp1(-/-) or apoER2(-/-) mice developed severe neurodegeneration caused by mild selenium deficiency, brain selenium was similar to 35 ng/g. In extreme selenium deficiency, however, brain selenium of similar to 12 ng/g was tolerated when both Sepp1 and apoER2 were intact in the brain. These findings indicate that tandem Sepp1-apoER2 interactions supply selenium for maintenance of brain neurons. One interaction is at the blood-brain barrier, and the other is within the brain. We postulate that Sepp1 inside the blood-brain barrier is taken up by neurons via apoER2, concentrating brain selenium in them.-Burk, R. F., Hill, K. E., Motley, A. K., Winfrey, V. P., Kurokawa, S., Mitchell, S. L., Zhang, W. Selenoprotein P and apolipoprotein E receptor-2 interact at the blood-brain barrier and also within the brain to maintain an essential selenium pool that protects against neurodegeneration.