Bialowas-McGoey Lynn A, Lesicka Agnieszka, Whitaker-Azmitia Patricia M
Department of Psychology, Stony Brook University, Stony Brook, New York, USA.
Glia. 2008 Dec;56(16):1780-90. doi: 10.1002/glia.20727.
S100B is a calcium-binding protein released by astroglial cells of the brain capable of producing numerous extracellular effects. Although the direct molecular mechanism remains unknown, these effects can be trophic including differentiation, growth, recovery, and survival of neurons when the S100B protein is mainly oxidized and neurotoxic including apoptosis and neuroinflammatory processes marked by microglial activation when in a reduced state. S100B and its receptor RAGE (receptor for advanced glycation end products) have been found to be increased in Alzheimer's disease, Down syndrome, with tissue trauma and ischemia. In the current study, we examined the binding of the S100B receptor (RAGE) on microglial cells and the developmental effects of the antioxidant vitamin E on microglial activation and the upregulation of RAGE in an S100B over-expressing mouse model of pathological aging. We report that RAGE is co-localized on activated microglial cells and vitamin E induced dramatic increases in microglial activation as well as total microglial relative optical density that was accompanied by upregulation of the RAGE receptor, particularly in the CA1 region of the hippocampus. Our findings suggest further investigation into the potential role of vitamin E in reducing the oxidation state of the S100B protein and its influence on neuroinflammatory processes marked by microglial activation in vivo.
S100B是一种由脑内星形胶质细胞释放的钙结合蛋白，能够产生多种细胞外效应。尽管直接的分子机制尚不清楚，但当S100B蛋白主要处于氧化状态时，这些效应可能具有营养作用，包括神经元的分化、生长、恢复和存活；而当处于还原状态时，则具有神经毒性作用，包括以小胶质细胞激活为特征的细胞凋亡和神经炎症过程。在阿尔茨海默病、唐氏综合征、组织创伤和缺血时，已发现S100B及其受体RAGE（晚期糖基化终产物受体）水平升高。在本研究中，我们在一个S100B过表达的病理性衰老小鼠模型中，检测了小胶质细胞上S100B受体（RAGE）的结合情况，以及抗氧化剂维生素E对小胶质细胞激活和RAGE上调的发育影响。我们报告称，RAGE与激活的小胶质细胞共定位，维生素E可显著增加小胶质细胞的激活以及小胶质细胞的总相对光密度，同时伴有RAGE受体的上调，尤其是在海马体的CA1区域。我们的研究结果表明，需要进一步研究维生素E在降低S100B蛋白氧化状态及其对体内以小胶质细胞激活为特征的神经炎症过程的影响方面的潜在作用。
