Arús Bernardo Assein, Souza Débora Guerini, Bellaver Bruna, Souza Diogo Onofre, Gonçalves Carlos-Alberto, Quincozes-Santos André, Bobermin Larissa Daniele
Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Mol Cell Biochem. 2017 Apr;428(1-2):67-77. doi: 10.1007/s11010-016-2917-5. Epub 2017 Jan 9.
Resveratrol is a dietary polyphenol that displays neuroprotective properties in several in vivo and in vitro experimental models, by modulating oxidative and inflammatory responses. Glutathione (GSH) is a key antioxidant in the central nervous system (CNS) that modulates several cellular processes, and its depletion is associated with oxidative stress and inflammation. Therefore, this study sought to investigate the protective effects of resveratrol against GSH depletion pharmacologically induced by buthionine sulfoximine (BSO) in C6 astroglial cells, as well as its underlying cellular mechanisms. BSO exposure resulted in several detrimental effects, decreasing glutamate-cysteine ligase (GCL) activity, cystine uptake, GSH intracellular content and the activities of the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR). Moreover, BSO increased reactive oxygen/nitrogen species (ROS/RNS) levels and pro-inflammatory cytokine release. Resveratrol prevented these effects by protecting astroglial cells against BSO-induced cytotoxicity, by modulating oxidative and inflammatory responses. Additionally, we observed that pharmacological inhibition of heme oxygenase 1 (HO-1), an essential cellular defense against oxidative and inflammatory injuries, abolished all the protective effects of resveratrol. These observations suggest HO-1 pathway as a cellular effector in the mechanism by which resveratrol protects astroglial cells against GSH depletion, a condition that may be associated to neurodegenerative diseases.
白藜芦醇是一种膳食多酚，通过调节氧化和炎症反应，在多种体内和体外实验模型中表现出神经保护特性。谷胱甘肽（GSH）是中枢神经系统（CNS）中的一种关键抗氧化剂，可调节多种细胞过程，其耗竭与氧化应激和炎症相关。因此，本研究旨在探讨白藜芦醇对丁硫氨酸亚砜胺（BSO）在C6星形胶质细胞中诱导的GSH耗竭的保护作用及其潜在的细胞机制。暴露于BSO会导致多种有害影响，降低谷氨酸-半胱氨酸连接酶（GCL）活性、胱氨酸摄取、GSH细胞内含量以及抗氧化酶谷胱甘肽过氧化物酶（GPx）和谷胱甘肽还原酶（GR）的活性。此外，BSO会增加活性氧/氮物种（ROS/RNS）水平和促炎细胞因子的释放。白藜芦醇通过调节氧化和炎症反应，保护星形胶质细胞免受BSO诱导的细胞毒性，从而预防了这些影响。此外，我们观察到，血红素加氧酶1（HO-1）是细胞抵御氧化和炎症损伤的重要防御机制，其药理学抑制作用消除了白藜芦醇的所有保护作用。这些观察结果表明，HO-1途径是白藜芦醇保护星形胶质细胞免受GSH耗竭的机制中的一种细胞效应器，而GSH耗竭这种情况可能与神经退行性疾病有关。
