Tocotrienol Affects Oxidative Stress, Cholesterol Homeostasis and the Amyloidogenic Pathway in Neuroblastoma Cells: Consequences for Alzheimer's Disease.
Tocotrienol Affects Oxidative Stress, Cholesterol Homeostasis and the Amyloidogenic Pathway in Neuroblastoma Cells: Consequences for Alzheimer's Disease.
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DOI：
10.3390/ijms17111809
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发表时间：
2016-10-29
影响因子：
5.6
通讯作者：
Hartmann T
中科院分区：
文献类型：
--
作者：
Grimm MO;Regner L;Mett J;Stahlmann CP;Schorr P;Nelke C;Streidenberger O;Stoetzel H;Winkler J;Zaidan SR;Thiel A;Endres K;Grimm HS;Volmer DA;Hartmann T
阿尔茨海默病（AD）的特征之一是淀粉样蛋白负荷增加和活性氧（ROS）水平升高。众所周知，维生素E具有有益的神经保护作用，以前，一些研究表明，由于维生素E的抗氧化特性，它与降低AD风险有关。然而，流行病学研究和维生素E治疗的营养方法存在争议。本文研究了α-生育三烯醇（α-tocotrienol）在神经细胞系ad相关过程中的作用，α-生育三烯醇属于维生素E的一类。与文献一致，α-生育三烯醇降低了SH-SY5Y细胞的ROS水平。在生育三烯醇存在的情况下，胆固醇和胆固醇酯（已被证明是AD的危险因素）降低了。除了生育三烯醇的明显积极作用外，淀粉样蛋白-β (Aβ)水平的增加还伴随着Aβ生成酶活性的增加。分泌酶及其成分的蛋白质和基因表达保持不变，而在无细胞试验中，生育三烯醇加速酶的活性。除了促进Aβ的产生外，生育三烯醇还抑制了神经2a （N2a）细胞中Aβ的降解。我们的研究结果可能有助于理解维生素E研究中有争议的发现，并证明除了已知的积极神经保护特性外，生育三烯醇在AD方面也有负面特征。
One of the characteristics of Alzheimer´s disease (AD) is an increased amyloid load and an enhanced level of reactive oxidative species (ROS). Vitamin E has known beneficial neuroprotective effects, and previously, some studies suggested that vitamin E is associated with a reduced risk of AD due to its antioxidative properties. However, epidemiological studies and nutritional approaches of vitamin E treatment are controversial. Here, we investigate the effect of α-tocotrienol, which belongs to the group of vitamin E, on AD-relevant processes in neuronal cell lines. In line with the literature, α-tocotrienol reduced the ROS level in SH-SY5Y cells. In the presence of tocotrienols, cholesterol and cholesterol esters, which have been shown to be risk factors in AD, were decreased. Besides the unambiguous positive effects of tocotrienol, amyloid-β (Aβ) levels were increased accompanied by an increase in the activity of enzymes responsible for Aβ production. Proteins and gene expression of the secretases and their components remained unchanged, whereas tocotrienol accelerates enzyme activity in cell-free assays. Besides enhanced Aβ production, tocotrienols inhibited Aβ degradation in neuro 2a (N2a)-cells. Our results might help to understand the controversial findings of vitamin E studies and demonstrate that besides the known positive neuroprotective properties, tocotrienols also have negative characteristics with respect to AD.
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