Oxidative stress induces apolipoprotein D overexpression in hippocampus during aging and Alzheimer's disease.
Oxidative stress induces apolipoprotein D overexpression in hippocampus during aging and Alzheimer's disease.
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DOI：
10.3233/jad-130215
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发表时间：
2013
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影响因子：
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通讯作者：
E. Mártínez;A. Navarro;C. Ordóñez;E. D. Del Valle;J. Tolivia
中科院分区：
文献类型：
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作者：
E. Mártínez;A. Navarro;C. Ordóñez;E. D. Del Valle;J. Tolivia
载脂蛋白D（Apo D）是一种脂质结合蛋白，其表达在衰老和年龄依赖性神经退行性疾病如阿尔茨海默病（AD）期间在哺乳动物脑中被强烈诱导，其中它可以作为神经保护和抗氧化蛋白发挥重要功能。越来越多的证据表明，随着年龄的增长，自由基和氧化应激的逐渐增加是大脑老化的主要决定因素。本工作的目的是研究过氧化氢（H2O2）在海马细胞中Apo D表达的影响，以探讨氧化应激和海马中发现的衰老和AD期间Apo D水平升高之间的关系，并阐明导致这种增加的可能途径。在这项研究中，我们证明，载脂蛋白D的表达在海马神经元的老年人和AD脑直接相关的与年龄相关的氧化应激增加。更重要的是，我们在HT22细胞系中的结果表明，Apo D蛋白水平以浓度依赖性方式增加，特别是在引起氧化损伤和凋亡性细胞死亡的H2O2浓度下。这些数据支持的想法，氧化应激诱导的细胞凋亡在老化和AD可能与在这些情况下的表达载脂蛋白D的增量。
Apolipoprotein D (Apo D) is a lipid binding protein whose expression is strongly induced in the mammalian brain during aging and age-dependent neurodegenerative diseases such as Alzheimer's disease (AD), where it can play an important function as a neuroprotective and antioxidant protein. Increasing evidence suggests that the gradual increase in free radicals and oxidative stress with age is the primary determinant to aging brain. The aim of this work is to study the effect of hydrogen peroxide (H2O2) in Apo D expression, in hippocampal cells, in order to investigate the relationship between oxidative stress and elevated levels of Apo D found in hippocampus during aging and AD and also elucidate the possible pathways that lead to this increase. In this study, we demonstrated that Apo D expression in hippocampal neurons of aged and AD brains directly correlates with age-related increase in oxidative stress. More importantly, our results in the HT22 cell line indicate that Apo D protein level increases in a concentration-dependent manner specifically at those H2O2 concentrations that caused oxidative damage and apoptotic cell death. These data support the idea that oxidative stress-induced apoptosis during aging and AD may be associated with the increment in the expression of Apo D in these situations.