Omotayo T I, Akinyemi G S, Omololu P A, Ajayi B O, Akindahunsi A A, Rocha J B T, Kade I J
Department of Biochemistry, Federal University of Technology, Akure, Ondo State, Nigeria.
Centro de Ciencias Naturais e Exatas, Programa Posgraduacao em Bioquimica Toxciologica, Universidade Federal de Santa Maria, RS, Brazil.
Redox Biol. 2015;4:234-41. doi: 10.1016/j.redox.2014.12.015. Epub 2014 Dec 24.
The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enzyme in Fe(2+)-mediated in vitro oxidative stress model. The results show that Fe(2+) inhibited the transmembrane enzyme in a concentration dependent manner and this effect was accompanied by a biphasic generation of aldehydic product of lipid peroxidation. While dithiothreitol prevented both Fe(2+) inhibitory effect on the pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not inhibition of the pump. Besides, malondialdehyde (MDA) inhibited the pump by a mechanism not related to oxidation of its critical thiols. Apparently, the low activity of the pump in degenerative diseases mediated by Fe(2+) may involve complex multi-component mechanisms which may partly involve an initial oxidation of the critical thiols of the enzyme directly mediated by Fe(2+) and during severe progression of such diseases; aldehydic products of lipid peroxidation such as MDA may further exacerbate this inhibitory effect by a mechanism that is likely not related to the oxidation of the catalytically essential thiols of the ouabain-sensitive cerebral electrogenic pump.
在自由基诱导的神经退行性疾病中，定义氧化应激在脑钠泵失活中复杂作用的精确分子事件尚未完全阐明，因此仍然是一个有待解决的问题。在此，我们在铁离子（Fe(2+)）介导的体外氧化应激模型中研究了脑跨膜生电酶活性的调节。结果表明，Fe(2+)以浓度依赖性方式抑制跨膜酶，并且这种效应伴随着脂质过氧化醛产物的双相生成。虽然二硫苏糖醇既能防止Fe(2+)对泵的抑制作用，又能防止脂质过氧化，但维生素E只能防止脂质过氧化，而不能防止泵的抑制。此外，丙二醛（MDA）通过一种与其关键硫醇氧化无关的机制抑制泵。显然，在由Fe(2+)介导的退行性疾病中，泵的低活性可能涉及复杂的多组分机制，其中部分可能涉及由Fe(2+)直接介导的酶关键硫醇的初始氧化，而在这些疾病的严重进展过程中，脂质过氧化的醛产物如MDA可能通过一种可能与哇巴因敏感的脑生电泵催化必需硫醇氧化无关的机制进一步加剧这种抑制作用。
