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白藜芦醇可保护H19-7海马神经元细胞免受β淀粉样蛋白诱导的氧化损伤及记忆相关蛋白损伤。

Resveratrol protects β amyloid-induced oxidative damage and memory associated proteins in H19-7 hippocampal neuronal cells.

作者信息

Rege Shraddha D, Geetha Thangiah, Broderick Tom L, Babu Jeganathan Ramesh

机构信息

Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL 36849, USA.

出版信息

Curr Alzheimer Res. 2015;12(2):147-56. doi: 10.2174/1567205012666150204130009.

Abstract

Resveratrol (trans-3, 5, 4'-trihydroxystilbene) is a polyphenolic phytoalexin known to exhibit antioxidant and neuroprotective effects in several experimental models. Amyloid β peptide (Aβ), a core component of extracellular senile plaques accumulates in the brains of patients with Alzheimer's disease and is related to the development of cognitive impairment and neuronal loss. The present study evaluates the neuroprotective action of resveratrol on Aβ-induced oxidative stress and memory loss. Cultured rat hippocampal H19-7 neuronal cell line was pretreated with 75 μM of resveratrol for 2 hrs followed by 25 μM of Aβ (1-40) for 24 hrs. H19-7 cells treated with Aβ exhibited increased lipid peroxide levels. Enzymatic antioxidants including superoxide dismutase, catalase, glutathione reductase, and non-enzymatic antioxidants such as tocopherol, ascorbic acid and glutathione were decreased in the Aβ treated group when compared to the control group. Aβ treatment also increased the expression of total tau as well as phosphorylated forms of tau (CP13, S202/205; PHF1, S396/404) and decreased the expression of insulin degrading enzyme (IDE), phosphoglycogen synthase kinase 3β involved in Aβ degradation and tau hyper phosphorylation. Expression of PSD-95 and Arc proteins, essential for synaptic maturity and plasticity, was decreased by Aβ treatment. Resveratrol treatment attenuated the accumulation of lipid peroxide levels, up-regulated the antioxidant activities and improved the expression of memory-associated proteins in Aβ treated H19-7 cells. These findings highlight the neuroprotective effect of resveratrol in preventing Aβ-induced oxidative damage and memory loss in vitro.

摘要

白藜芦醇(反式 - 3,5,4'-三羟基二苯乙烯)是一种多酚类植物抗毒素,已知在多种实验模型中具有抗氧化和神经保护作用。淀粉样β肽(Aβ)是细胞外老年斑的核心成分,在阿尔茨海默病患者的大脑中积累,与认知障碍和神经元丢失的发展有关。本研究评估了白藜芦醇对Aβ诱导的氧化应激和记忆丧失的神经保护作用。用75μM白藜芦醇预处理培养的大鼠海马H19-7神经元细胞系2小时,然后用25μM Aβ(1-40)处理24小时。用Aβ处理的H19-7细胞脂质过氧化物水平升高。与对照组相比,Aβ处理组中包括超氧化物歧化酶、过氧化氢酶、谷胱甘肽还原酶在内的酶促抗氧化剂以及生育酚、抗坏血酸和谷胱甘肽等非酶促抗氧化剂均减少。Aβ处理还增加了总tau以及tau的磷酸化形式(CP13,S202/205;PHF1,S396/404)的表达,并降低了参与Aβ降解和tau过度磷酸化的胰岛素降解酶(IDE)、磷酸糖原合酶激酶3β的表达。对突触成熟和可塑性至关重要的PSD-95和Arc蛋白的表达因Aβ处理而降低。白藜芦醇处理减弱了脂质过氧化物水平的积累,上调了抗氧化活性,并改善了Aβ处理的H19-7细胞中记忆相关蛋白的表达。这些发现突出了白藜芦醇在体外预防Aβ诱导的氧化损伤和记忆丧失方面的神经保护作用。

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