Early induction of oxidative stress in a mouse model of Alzheimer's disease with heme oxygenase activity.
Early induction of oxidative stress in a mouse model of Alzheimer's disease with heme oxygenase activity.
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DOI：
10.3892/mmr.2014.2252
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发表时间：
2014-08
影响因子：
3.4
通讯作者：
Yu Z
中科院分区：
文献类型：
--
作者：
Xing S;Shen D;Chen C;Wang J;Yu Z
有证据表明阿尔茨海默病（Alzheimer's disease，AD）患者的脑组织容易受到氧化应激的攻击，大量研究表明血红素加氧酶（heme oxygenase，HO）是细胞对应激的主要适应性反应。然而，HO-1和HO-2在这一过程中是否发挥了不同的作用尚未得到研究。在本研究中，在AD模型中显示HO-1和HO-2在AD的早期阶段具有不同的作用。采用Morris水迷宫测试APP swe/PS1ΔE9（APP/PS1）转基因小鼠和野生型小鼠的学习记忆能力。使用免疫荧光染色测量β-淀粉样蛋白斑块。活性氧（ROS）水平的变化，用荧光技术测量的Escherichia campi。结果表明，与野生型小鼠相比，APP/PS1转基因小鼠的逃避潜伏期、淀粉样斑块沉积和活性氧产生增加。此外，使用双重免疫荧光染色和western blot分析，发现HO-1和HO-2在APP/PS 1小鼠的大脑中的表达增加，特别是，HO-2也被发现在星形胶质细胞中过表达。两组间血浆HO-1浓度差异不大，而ELISA显示APP/PS1小鼠的血浆HO-2浓度低于野生型小鼠。总之，HO-2的过度表达是一个早期事件，并在AD的进展中起着更关键的作用。
Evidence suggests that brain tissues of patients with Alzheimer’s disease (AD) are easily attacked by oxidative stress, and numerous studies indicate that heme oxygenase (HO) is a major cell adaptive responder to stress. However, whether HO-1 and HO-2 play different roles in this process has not yet been studied. In the present study, it was shown in an AD model that HO-1 and HO-2 have different roles in the early stages of AD. Learning and memory ability was tested in APPswe/PS1ΔE9 (APP/PS1) transgenic and wild-type mice using the Morris water maze. β-amyloid plaques were measured using immunofluorescence staining. Changes in reactive oxygen species (ROS) levels in the hippocampi were measured using a fluorescence technique. The results indicated that the escape latency, amyloid plaque deposition and ROS production increased in the hippocampi of APP/PS1 transgenic mice compared with wild-type mice. Furthermore, using double-immunofluorescence staining and western blot analysis, it was found that the expression of HO-1 and HO-2 increased in the hippocampi of APP/PS1 mice and, notably, HO-2 was also found to be overexpressed in astrocytes. Little difference was observed in the plasma HO-1 concentrations between the two groups, while the plasma HO-2 concentration of the APP/PS1 mice was lower than that of the wild-type mice, shown by ELISA. In conclusion, HO-2 overexpression is an early event and plays a more critical role in the progression of AD.
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影响因子：
6.1
作者：
Maes, Olivier C.;Kravitz, Steven;Schipper, Hyman M.
通讯作者：
Schipper, Hyman M.
影响因子：
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作者：
Feng Y;Wang X
通讯作者：
Wang X
影响因子：
20.1
作者：
Ishikawa, M;Kajimura, M;Suematsu, M
通讯作者：
Suematsu, M
影响因子：
11.2
作者：
SCHIPPER, HM;STOPA, EG
通讯作者：
STOPA, EG
影响因子：
2.9
作者：
Vreman, HJ;Wong, RJ;Stevenson, DK
通讯作者：
Stevenson, DK