Departamento de Nutrición y Bromatología, Toxicología y Medicina Legal, Área de Nutrición y Bromatología, Facultad de Farmacia, Universidad de Sevilla, C/Profesor Garcia Gonzalez, 2, 41012, Sevilla, Spain.
MIB, Unité de Recherche Œnologie, EA4577, USC 1366 INRA, ISVV, Université de Bordeaux, Bordeaux, France.
Food Chem Toxicol. 2019 Dec;134:110817. doi: 10.1016/j.fct.2019.110817. Epub 2019 Sep 12.
Preventing the abnormal assembly of α-synuclein (α-Syn) and the correct modulation of vitagenes system exercise strong neuroprotective effects. It has been reported that melatonin (MEL), protocatechuic acid (PCA) and hydroxytyrosol (HT) reduce α-Syn toxicity. Their effect on the vitagenes system of PC12 cells have not been explored yet. These bioactive can cross the blood brain barrier (BBB). Therefore, this work aims to evaluate the inhibitory and destabilising capacities of MEL, PCA, HT, and their combinations on α-Syn kinetics and effects on vitagenes system (sirtuin-1 (SIRT-1), sirtuin-2 (SIRT-2), heme oxygenase (HO-1) and heat shock protein 70 (Hsp-70)). In vitro techniques (Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis, MTT assay and qPCR) were used. Compounds, both individually and simultaneously were able to decrease the toxicity induced by α-Syn. Concurrently, occurrence of PCA (100 μM) +HT (100 μM) showed the highest inhibitory effect against α-Syn fibril formation and destabilisation of α-Syn fibrils (88 and 62%, respectively). Moreover, these compounds increased the expression of SIRT-2, HO-1 and Hsp70, contributing to a neuroprotective effect. In addition, the most important result is the increase on the expression of SIRT-2 caused by the combination of MEL + HT + PCA in the absence of α-Syn fibrils.
预防α-突触核蛋白（α-Syn）的异常聚集和正确调节维生素基因系统具有很强的神经保护作用。据报道，褪黑素（MEL）、原儿茶酸（PCA）和羟基酪醇（HT）可降低α-Syn 的毒性。它们对 PC12 细胞维生素基因系统的影响尚未被探索。这些生物活性物质可以穿过血脑屏障（BBB）。因此，这项工作旨在评估 MEL、PCA、HT 及其组合对 α-Syn 动力学的抑制和去稳定能力，以及它们对维生素基因系统（SIRT-1、SIRT-2、血红素加氧酶（HO-1）和热休克蛋白 70（Hsp-70））的影响。使用了体外技术（硫黄素 T（ThT）、透射电子显微镜（TEM）、电泳、MTT 测定和 qPCR）。单独和同时使用化合物均能降低α-Syn 诱导的毒性。同时，PCA（100μM）+HT（100μM）的出现对α-Syn 纤维形成表现出最高的抑制作用，并对α-Syn 纤维的去稳定化作用分别达到 88%和 62%。此外，这些化合物增加了 SIRT-2、HO-1 和 Hsp70 的表达，有助于发挥神经保护作用。此外，最重要的结果是在没有α-Syn 纤维的情况下，MEL+HT+PCA 的组合增加了 SIRT-2 的表达。
