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Sulforaphane induces Nrf2 target genes and attenuates inflammatory gene expression in microglia from brain of young adult and aged mice

机译:萝卜硫烷诱导成年小鼠和成年小鼠脑中小胶质细胞中Nrf2靶基因并减弱炎症基因表达

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摘要

Increased neuroinflammation and oxidative stress resulting from heightened microglial activation are associated with age-related cognitive impairment. The objectives of this study were to examine the effects of the bioactive sulforaphane (SFN) on the nuclear factor E2-related factor 2 (Nrf2) pathway in BV2 microglia and primary microglia, and to evaluate proinflammatory cytokine expression in lipopolysaccharide (LPS)-stimulated primary microglia from adult and aged mice. BV2 microglia and primary microglia isolated from young adult and aged mice were treated with SFN and LPS. Changes in Nrf2 activity, expression of Nrf2 target genes, and levels of proinflammatory markers were assessed by quantitative PCR and immunoassay. SFN increased Nrf2 DNA-binding activity and upregulated Nrf2 target genes in BV2 microglia, while reducing LPS-induced interleukin (IL-)1 beta, IL-6, and inducible nitric oxide synthase (iNOS). In primary microglia from adult and aged mice, SFN increased expression of Nrf2 target genes and attenuated IL-1 beta, IL-6, and iNOS induced by LPS. These data indicate that SFN is a potential beneficial supplement that may be useful for reducing microglial mediated neuroinflammation and oxidative stress associated with aging. (C) 2015 Elsevier Inc. All rights reserved.
机译:由小胶质细胞活化增加引起的神经炎症和氧化应激增加与年龄相关的认知障碍有关。这项研究的目的是检查生物活性萝卜硫素(SFN)对BV2小胶质细胞和原发性小胶质细胞核因子E2相关因子2(Nrf2)途径的影响,并评估脂多糖(LPS)刺激的促炎细胞因子表达。成人和老年小鼠的原发性小胶质细胞。用SFN和LPS处理从成年和老年小鼠中分离的BV2小胶质细胞和原发性小胶质细胞。通过定量PCR和免疫测定评估Nrf2活性,Nrf2靶基因的表达和促炎标志物水平的变化。 SFN在BV2小胶质细胞中增加了Nrf2 DNA结合活性并上调了Nrf2目标基因,同时降低了LPS诱导的白介素(IL-)1 beta,IL-6和诱导型一氧化氮合酶(iNOS)。在成年和成年小鼠的原发性小胶质细胞中,SFN增加了Nrf2靶基因的表达,并减弱了LPS诱导的IL-1 beta,IL-6和iNOS。这些数据表明,SFN是潜在的有益补充剂,可用于减少与衰老相关的小胶质细胞介导的神经炎症和氧化应激。 (C)2015 Elsevier Inc.保留所有权利。

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