Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Cell Mol Neurobiol. 2022 Apr;42(3):829-846. doi: 10.1007/s10571-020-00981-5. Epub 2020 Oct 20.
Sulforaphane is a natural compound that presents anti-inflammatory and antioxidant properties, including in the central nervous system (CNS). Astroglial cells are involved in several functions to maintain brain homeostasis, actively participating in the inflammatory response and antioxidant defense systems. We, herein, investigated the potential mechanisms involved in the glioprotective effects of sulforaphane in the C6 astrocyte cell line, when challenged with the inflammogen, lipopolysaccharide (LPS). Sulforaphane prevented the LPS-induced increase in the expression and/or release of pro-inflammatory mediators, possibly due to nuclear factor κB and hypoxia-inducible factor-1α activation. Sulforaphane also modulated the expressions of the Toll-like and adenosine receptors, which often mediate inflammatory processes induced by LPS. Additionally, sulforaphane increased the mRNA levels of nuclear factor erythroid-derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO1), both of which mediate several cytoprotective responses. Sulforaphane also prevented the increase in NADPH oxidase activity and the elevations of superoxide and 3-nitrotyrosine that were stimulated by LPS. In addition, sulforaphane and LPS modulated superoxide dismutase activity and glutathione metabolism. Interestingly, the anti-inflammatory and antioxidant effects of sulforaphane were blocked by HO1 pharmacological inhibition, suggesting its dependence on HO1 activity. Finally, in support of a glioprotective role, sulforaphane prevented the LPS-induced decrease in glutamate uptake, glutamine synthetase activity, and glial-derived neurotrophic factor (GDNF) levels, as well as the augmentations in S100B release and Na, K ATPase activity. To our knowledge, this is the first study that has comprehensively explored the glioprotective effects of sulforaphane on astroglial cells, reinforcing the beneficial effects of sulforaphane on astroglial functionality.
萝卜硫素是一种天然化合物，具有抗炎和抗氧化特性，包括在中枢神经系统 (CNS) 中。星形胶质细胞参与维持脑内环境稳定的多种功能，积极参与炎症反应和抗氧化防御系统。我们在此研究了萝卜硫素在 C6 星形胶质细胞系中对神经胶质细胞的保护作用的潜在机制，当受到炎症原脂多糖 (LPS) 挑战时。萝卜硫素可防止 LPS 诱导的促炎介质表达和/或释放增加，这可能是由于核因子 κB 和缺氧诱导因子-1α 的激活。萝卜硫素还调节 Toll 样和腺苷受体的表达，这些受体通常介导 LPS 诱导的炎症过程。此外，萝卜硫素增加了核因子红细胞衍生 2 样 2 (Nrf2) 和血红素加氧酶-1 (HO1) 的 mRNA 水平，两者均介导多种细胞保护反应。萝卜硫素还可防止 LPS 刺激引起的 NADPH 氧化酶活性增加以及超氧化物和 3-硝基酪氨酸升高。此外，萝卜硫素和 LPS 调节超氧化物歧化酶活性和谷胱甘肽代谢。有趣的是，HO1 药理学抑制阻断了萝卜硫素的抗炎和抗氧化作用，表明其依赖于 HO1 活性。最后，支持神经胶质保护作用，萝卜硫素可防止 LPS 诱导的谷氨酸摄取、谷氨酰胺合成酶活性和神经胶质衍生神经营养因子 (GDNF) 水平降低，以及 S100B 释放和 Na+，K+-ATP 酶活性增加。据我们所知，这是第一项全面研究萝卜硫素对星形胶质细胞的神经胶质保护作用的研究，这加强了萝卜硫素对星形胶质细胞功能的有益作用。
