The influence of chronic ibuprofen treatment on proteins expressed in the mouse hippocampus.
The influence of chronic ibuprofen treatment on proteins expressed in the mouse hippocampus.
复制标题
长期布洛芬治疗对小鼠海马蛋白表达的影响。
DOI：
10.1016/j.ejphar.2015.01.047
复制
发表时间：
2015
影响因子：
5
通讯作者：
Shogo Matsuyama
中科院分区：
文献类型：
--
作者：
Kenji Matsuura;Mieko Otani;Masaoki Takano;Keiichi Kadoyama;Shogo Matsuyama
布洛芬是一种非甾体抗炎药（NSAID），在流行病学和临床研究中已经证明，使用布洛芬治疗可以延缓发病，减缓认知能力下降，降低阿尔茨海默病（AD）的发病率。然而，对其作用机制的全面了解仍不清楚。为了阐明布洛芬对阿尔茨海默病学习和记忆障碍的预防作用，我们使用二维凝胶电泳（2-DE）和质谱法对慢性布洛芬治疗小鼠的海马进行了蛋白质组学分析。经鉴定，慢性布洛芬治疗小鼠海马中28个蛋白和7个磷酸化蛋白发生显著变化：翻译控制肿瘤蛋白、硫氧还蛋白依赖的过氧化物还原酶和过氧化物还蛋白6升高，胶质纤维酸性蛋白、二氢嘧啶酶相关蛋白2、EF-hand结构域蛋白D2和14-3-3ζ降低。这些鉴定的蛋白和磷酸化蛋白可分为细胞骨架、神经元发育、伴侣、代谢、凋亡、神经递质释放、ATP合成酶、去泛素化、蛋白酶体、NOS抑制剂、转接器、囊泡转运、信号转导、抗氧化酶、质子转运、突触发生和丝氨酸/苏氨酸磷酸酶等类型。Western blot分析显示慢性布洛芬治疗小鼠海马组织中二氢嘧啶酶相关蛋白2、热休克蛋白8、泛素羧基末端水解酶PGP9.5、γ烯醇化酶水平的变化。这些发现表明，布洛芬的慢性治疗改变了海马中一些蛋白质和磷酸化蛋白的水平。我们认为这些鉴定的蛋白和磷酸化蛋白在降低阿尔茨海默病的发病率，特别是学习和记忆功能受损方面发挥重要作用。
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), treatment with which has been shown to delay the onset, slows the cognitive decline, and decreases the incidence of Alzheimer׳s disease (AD) in epidemiological and clinical studies. However, a comprehensive understanding of its mechanism of action remains unclear. To elucidate the prophylactic effect of ibuprofen on the onset of the learning and memory disturbances of AD, we performed proteomic analysis of the hippocampus of chronic ibuprofen-treated mice using two-dimensional gel electrophoresis (2-DE) followed by mass spectrometry. Twenty-eight proteins and seven phosphoproteins were identified to be significantly changed in the hippocampus of chronic ibuprofen-treated mice: translationally controlled tumor protein, thioredoxin-dependent peroxide reductase, and peroxiredoxin 6 were increased, and glial fibrillary acidic protein, dihydropyrimidinase-related protein 2, EF-hand domain-containing protein D2, and 14-3-3ζ were decreased. These identified proteins and phosphoproteins could be classified as cytoskeletal, neuronal development, chaperone, metabolic, apoptosis, neurotransmitter release, ATP synthase, deubiquitination, proteasome, NOS inhibitor, adapter, vesicle transport, signal transduction, antioxidant enzyme, proton transport, synaptogenesis, and serine/threonine phosphatase types. Western blot analysis showed the changes in dihydropyrimidinase-related protein 2, heat shock protein 8, ubiquitin carboxyl-terminal hydrolase PGP9.5, and γ-enolase levels in the hippocampus of chronic ibuprofen-treated mice. These findings showed that the chronic treatment with ibuprofen changed the levels of some proteins and phosphoproteins in the hippocampus. We propose that these identified proteins and phosphoproteins play an important role in decreasing the incidence of AD, especially impaired learning and memory functions.