Glutamine Improves Oxidative Stress through the Wnt3a/-Catenin Signaling Pathway in Alzheimer's Disease In Vitro and In Vivo
Glutamine Improves Oxidative Stress through the Wnt3a/-Catenin Signaling Pathway in Alzheimer's Disease In Vitro and In Vivo
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DOI：
10.1155/2019/4690280
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发表时间：
2019-01-01
影响因子：
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通讯作者：
Liu, Zhibin
中科院分区：
文献类型：
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作者：
Wang, Yuan;Wang, Qiang;Liu, Zhibin
背景/目标。阿尔茨海默病（AD）是最常见的神经退行性疾病，所有在该领域工作的研究人员都认为氧化应激与阿尔茨海默病密切相关。在这项研究中，我们假设谷氨酰胺（Gln）提供保护SAMP 8小鼠的氧化应激损伤以及潜在的机制。方法. SAMP 8小鼠连续8周灌胃谷氨酰胺，以评价谷氨酰胺对AD小鼠氧化应激的保护作用，其机制涉及Wnt 3a/-catenin信号通路。此外，大鼠嗜铬细胞瘤肿瘤细胞系PC 12用32 M谷氨酰胺预处理2 h，然后用40 M A25-35孵育24 h，以获得体外数据。结果在体内，谷氨酰胺的管理被发现改善行为缺陷和神经元损伤，增加超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-XP）的活性，降低丙二醛（MDA）的含量，并激活Wnt 3a/-连环蛋白信号通路在SAMP 8小鼠。体外谷氨酰胺处理可降低A25-35对PC 12细胞的毒性，抑制细胞凋亡。此外，谷氨酰胺处理增加SOD和GSH-XP活性，降低MDA含量，增加Wnt 3a和β-catenin蛋白水平。有趣的是，DKK-1（Wnt 3a/β-catenin途径抑制剂）降低了A25-35处理的PC 12细胞中谷氨酰胺的抗氧化能力。结论本研究提示谷氨酰胺可通过Wnt 3a/β-catenin信号通路保护AD小鼠免受氧化应激诱导的损伤。
Background/Aims. Alzheimer's disease (AD) is the most common neurodegenerative disease, and all researchers working in this field agree that oxidative stress is intimately associated with Alzheimer disease. In this study, we hypothesized that glutamine (Gln) offers protection against oxidative stress injury in SAMP8 mice as well as the underlying mechanism. Methods. The SAMP8 mice received glutamine intragastrically for 8 consecutive weeks to evaluate the protective effect of glutamine on oxidative stress in AD mice involving Wnt3a/-catenin signaling pathway. In addition, rat pheochromocytoma tumor cell line PC12 was pretreated with 32 M glutamine for 2 h followed by 24 h incubation with 40 M A25-35 to obtain in vitro data. Results. In vivo the administration of glutamine was found to ameliorate behavioral deficits and neuron damage, increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-XP) activity, reduce the malondialdehyde (MDA) content, and activate the Wnt3a/-catenin signaling pathway in SAMP8 mice. In vitro glutamine treatment decreased the toxicity of A25-35 on PC12 cells and prevented apoptosis. Additionally, glutamine treatment increased SOD and GSH-XP activity and decreased MDA content and increased Wnt3a and -catenin protein levels. Interestingly, the DKK-1 (Wnt3a/-catenin pathway inhibitor) decreased the antioxidant capacity of glutamine in A25-35-treated PC12 cells. Conclusion. This study suggests that glutamine could protect against oxidative stress-induced injury in AD mice via the Wnt3a/-catenin signaling pathway.