Díaz Mario, Valdés-Baizabal Catalina, de Pablo Daniel Pereda, Marin Raquel
Department of Physics, Faculty of Sciences, University of La Laguna, 38200 Tenerife, Spain.
Instituto Universitario de Neurociencias (IUNE), University of La Laguna, 38320 Tenerife, Spain.
Antioxidants (Basel). 2024 Feb 6;13(2):206. doi: 10.3390/antiox13020206.
The brain has a high metabolism rate that may generate reactive oxygen and nitrogen species. Consequently, nerve cells require highly efficient antioxidant defenses in order to prevent a condition of deleterious oxidative stress. This is particularly relevant in the hippocampus, a highly complex cerebral area involved in processing superior cognitive functions. Most current evidence points to hippocampal oxidative damage as a causal effect for neurodegenerative disorders, especially Alzheimer's disease. Nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) is a master key for the transcriptional regulation of antioxidant and detoxifying systems. It is ubiquitously expressed in brain areas, mainly supporting glial cells. In the present study, we have analyzed the relationships between Nrf2 and Keap1 isoforms in hippocampal tissue in response to aging and dietary long-chain polyunsaturated fatty acids (LCPUFA) supplementation. The possible involvement of lipoxidative and nitrosative by-products in the dynamics of the Nrf2/Keap1 complex was examined though determination of protein adducts, namely malondialdehyde (MDA), 4-hydroxynonenal (HNE), and 3-nitro-tyrosine (NTyr) under basal conditions. The results were correlated to the expression of target proteins heme-oxygenase-1 (HO-1) and glutathione peroxidase 4 (GPx4), whose expressions are known to be regulated by Nrf2/Keap1 signaling activation. All variables in this study were obtained simultaneously from the same preparations, allowing multivariate approaches. The results demonstrate a complex modification of the protein expression patterns together with the formation of adducts in response to aging and diet supplementation. Both parameters exhibited a strong interaction. Noticeably, LCPUFA supplementation to aged animals restored the Nrf2/Keap1/target protein patterns to the status observed in young animals, therefore driving a "rejuvenation" of hippocampal antioxidant defense.
大脑具有较高的代谢率，可能会产生活性氧和氮物质。因此，神经细胞需要高效的抗氧化防御机制，以防止有害的氧化应激状态。这在海马体中尤为重要，海马体是一个高度复杂的脑区，参与高级认知功能的处理。目前的大多数证据表明，海马体氧化损伤是神经退行性疾病，尤其是阿尔茨海默病的因果效应。核因子红细胞2相关因子2/ Kelch样ECH相关蛋白1（Nrf2/Keap1）是抗氧化和解毒系统转录调控的关键。它在脑区广泛表达，主要支持神经胶质细胞。在本研究中，我们分析了海马组织中Nrf2和Keap1亚型在衰老和饮食补充长链多不饱和脂肪酸（LCPUFA）时的关系。通过在基础条件下测定蛋白质加合物，即丙二醛（MDA）、4-羟基壬烯醛（HNE）和3-硝基酪氨酸（NTyr），研究了脂氧化和亚硝化副产物在Nrf2/Keap1复合物动态变化中的可能作用。结果与靶蛋白血红素加氧酶-1（HO-1）和谷胱甘肽过氧化物酶4（GPx4）的表达相关，已知它们的表达受Nrf2/Keap1信号激活的调节。本研究中的所有变量均从相同的制剂中同时获得，允许采用多变量方法。结果表明，随着衰老和饮食补充，蛋白质表达模式发生了复杂的改变，并伴有加合物的形成。这两个参数表现出强烈的相互作用。值得注意的是，给老年动物补充LCPUFA可使Nrf2/Keap1/靶蛋白模式恢复到年轻动物中观察到的状态，从而推动海马体抗氧化防御的“年轻化”。
