Means John C, Gerdes Bryan C, Koulen Peter
Vision Research Center, Department of Ophthalmology, School of Medicine, University of Missouri-Kansas City, 2411 Holmes St., Kansas City, MO 64108, USA.
Department of Biomedical Sciences, School of Medicine, University of Missouri-Kansas City, 2411 Holmes St., Kansas City, MO 64108, USA.
Int J Mol Sci. 2017 Jul 14;18(7):1521. doi: 10.3390/ijms18071521.
The polyphenolic phytostilbene, -resveratrol, is found in high amounts in several types and tissues of plants, including grapes, and has been proposed to have beneficial effects in the central nervous system due to its activity as an antioxidant. The objective of the present study was to identify the mechanisms underlying the protective effects of resveratrol under conditions of oxidative stress or DNA damage, induced by the extracellularly applied oxidant, -butyl hydrogen peroxide, or UV-irradiation, respectively. In C6 glioma cells, a model system for glial cell biology and pharmacology, resveratrol was protective against both types of insult. Prevention of tau protein cleavage and of the formation of neurofibrillary tangles were identified as mechanisms of action of resveratrol-mediated protection in both paradigms of cellular damage. However, depending on the type of insult, resveratrol exerted its protective activity differentially: under conditions of chemically induced oxidative stress, inhibition of caspase activity, while with DNA damage, resveratrol regulated tau phosphorylation at Ser. Results advance our understanding of resveratrol's complex impact on cellular signaling pathway and contribute to the notion of resveratrol's role as a pleiotropic therapeutic agent.
多酚类植物芪化物——白藜芦醇，在包括葡萄在内的多种植物类型和组织中含量很高，由于其作为抗氧化剂的活性，已被认为对中枢神经系统有有益作用。本研究的目的是确定在分别由细胞外施加的氧化剂叔丁基过氧化氢或紫外线照射诱导的氧化应激或DNA损伤条件下，白藜芦醇保护作用的潜在机制。在C6胶质瘤细胞（一种用于胶质细胞生物学和药理学的模型系统）中，白藜芦醇对这两种损伤均具有保护作用。在两种细胞损伤模式中，预防tau蛋白裂解和神经原纤维缠结的形成被确定为白藜芦醇介导的保护作用的作用机制。然而，根据损伤类型的不同，白藜芦醇发挥其保护活性的方式也有所不同：在化学诱导的氧化应激条件下，它抑制半胱天冬酶活性，而在DNA损伤时，白藜芦醇调节Ser位点的tau磷酸化。这些结果增进了我们对白藜芦醇对细胞信号通路复杂影响的理解，并有助于支持白藜芦醇作为一种多效性治疗剂的观点。
