Carpéné Christian, Hasnaoui Mounia, Balogh Balázs, Matyus Peter, Fernández-Quintela Alfredo, Rodríguez Víctor, Mercader Josep, Portillo Maria P
Institut des Maladies Métaboliques et Cardiovasculaires, Institut National de la Santé et de la Recherche Médicale (INSERM U1048), I2MC, 31432 Toulouse Cedex 4, France; Université Paul Sabatier, I2MC-UPS, CHU Rangueil, 31432 Toulouse Cedex 4, France.
Department of Organic Chemistry, Semmelweiss University, Hőgyes Endre Utca 7, Budapest 1095, Hungary.
Oxid Med Cell Longev. 2016;2016:2427618. doi: 10.1155/2016/2427618. Epub 2016 Jan 5.
Resveratrol has been reported to inhibit monoamine oxidases (MAO). Many substrates or inhibitors of neuronal MAO interact also with other amine oxidases (AO) in peripheral organs, such as semicarbazide-sensitive AO (SSAO), known as primary amine oxidase, absent in neurones, but abundant in adipocytes. We asked whether phenolic compounds (resveratrol, pterostilbene, quercetin, and caffeic acid) behave as MAO and SSAO inhibitors. AO activity was determined in human adipose tissue. Computational docking and glucose uptake assays were performed in 3D models of human AO proteins and in adipocytes, respectively. Phenolic compounds fully inhibited the fluorescent detection of H2O2 generated during MAO and SSAO activation by tyramine and benzylamine. They also quenched H2O2-induced fluorescence in absence of biological material and were unable to abolish the oxidation of radiolabelled tyramine and benzylamine. Thus, phenolic compounds hampered H2O2 detection but did not block AO activity. Only resveratrol and quercetin partially impaired MAO-dependent [(14)C]-tyramine oxidation and behaved as MAO inhibitors. Phenolic compounds counteracted the H2O2-dependent benzylamine-stimulated glucose transport. This indicates that various phenolic compounds block downstream effects of H2O2 produced by biogenic or exogenous amine oxidation without directly inhibiting AO. Phenolic compounds remain of interest regarding their capacity to limit oxidative stress rather than inhibiting AO.
据报道,白藜芦醇可抑制单胺氧化酶(MAO)。许多神经元MAO的底物或抑制剂也与外周器官中的其他胺氧化酶(AO)相互作用,例如氨基脲敏感胺氧化酶(SSAO),即初级胺氧化酶,在神经元中不存在,但在脂肪细胞中大量存在。我们研究了酚类化合物(白藜芦醇、紫檀芪、槲皮素和咖啡酸)是否具有MAO和SSAO抑制剂的作用。在人体脂肪组织中测定了AO活性。分别在人AO蛋白的三维模型和脂肪细胞中进行了计算对接和葡萄糖摄取试验。酚类化合物完全抑制了酪胺和苄胺激活MAO和SSAO过程中产生的H2O2的荧光检测。它们还在没有生物材料的情况下淬灭了H2O2诱导的荧光,并且无法消除放射性标记的酪胺和苄胺的氧化。因此,酚类化合物阻碍了H2O2的检测,但没有阻断AO活性。只有白藜芦醇和槲皮素部分损害了MAO依赖的[(14)C] - 酪胺氧化,并表现为MAO抑制剂。酚类化合物抵消了H2O2依赖的苄胺刺激的葡萄糖转运。这表明各种酚类化合物阻断了生物源性或外源性胺氧化产生的H2O2的下游效应,而没有直接抑制AO。酚类化合物在限制氧化应激而非抑制AO方面的能力仍然值得关注。