Background

Aluminum is an environmental neurotoxin widely exposed to animals and humans. Studies have shown that Alzheimer's disease (AD) is characterized by abnormally phosphorylated tau and Aβ deposition, aluminum exposure can lead to abnormal phosphorylated tau and Aβ deposition. Numerous epidemiological data and studies have confirmed that ApoEε4 is a risk factor for AD. However, whether there is an interaction effect between aluminum and ApoEε4 has yet to be verified.

Methods

SH-SY5Y cells were exposed with AlCl₃ and transfected with ApoEε4 respectively. The experimental groups included the blank control group, the low dose group (200 μM AlCl₃), the medium dose group (400 μM AlCl₃), the high dose group (800 μM AlCl₃), empty plasmid group, ApoEε4 group and 400 μM AlCl₃+ApoEε4 group. The cell viability was determined by CCK-8 kit after transfection for 48 h.The contents of total tau proteins, tau-181, tau-231, tau-262, tau-396 and Aβ42, were determined by ELISA kit. The interaction between AlCl₃ and ApoEε4 was analyzed by factorial design.

Results

With the increase of aluminum exposure, SH-SY5Y cell viability decreased, and the expression of the total tau, tau-181, tau-231, tau-262, tau-396 and Aβ content increased. The viability of cells transfected with ApoEε4 is significantly lower than control group, and the expressions of total tau, tau-181, tau-231, tau-262, tau-396 and Aβ in ApoEε4 transfected cells were significantly higher than control group. The viability of cells treated with AlCl₃ plus ApoEε4 was lower than those treated with, either AlCl₃, or ApoEε4. The expression of total tau, tau-181, tau-231, tau-262, tau-396 and Aβ in the cells treated with AlCl₃ plus ApoEε4 were significantly higher than those in other groups (p < 0.05). Moreover, analyzing data based on the factorial design, there was existed an interaction between AlCl₃ and ApoEε4 (p < 0.05).

Conclusion

Al and ApoEε4 gene can cause morphological changes of SH-SY5Y cells, reduce cell activity, and have obvious cytotoxic effects, and increase the phosphorylation levels of tau and the deposition of Aβ increases. In the presence of both Al and ApoEε4 genes, the two factors interact with each other and show a synergistic effect.

中文翻译：

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铝与ApoEε4结合对Tau磷酸化和Aβ沉积的影响

背景

铝是一种广泛暴露于动物和人类的环境神经毒素。研究表明，阿尔茨海默病 (AD) 的特征是异常磷酸化的 tau 和 Aβ 沉积，铝暴露会导致异常磷酸化的 tau 和 Aβ 沉积。大量流行病学数据和研究证实，ApoEε4是 AD 的危险因素。但铝与ApoEε4之间是否存在相互作用效应还有待验证。

方法

SH-SY5Y细胞分别用AlCl ₃和ApoEε4转染。实验组包括空白对照组、低剂量组（200 μM AlCl ₃）、中剂量组（400 μM AlCl ₃）、高剂量组（800 μM AlCl ₃）、空质粒组、ApoEε4组和400 μM AlCl ₃ + ApoEε4基团。转染48 h后用CCK-8试剂盒测定细胞活力。用ELISA试剂盒测定总tau蛋白tau-181、tau-231、tau-262、tau-396和Aβ42的含量。AlCl ₃和ApoEε4之间的相互作用通过因子设计进行分析。

结果

随着铝暴露的增加，SH-SY5Y细胞活力降低，总tau、tau-181、tau-231、tau-262、tau-396和Aβ含量的表达增加。ApoEε4转染细胞活力显着低于对照组，ApoEε4转染细胞中总tau、tau-181、tau-231、tau-262、tau-396和Aβ的表达显着高于对照组。用AlCl ₃加ApoEε4处理的细胞的活力低于用AlCl ₃或ApoEε4处理的细胞。AlCl ₃加ApoEε4处理的细胞中总tau、tau-181、tau-231、tau-262、tau-396和Aβ的表达显着高于其他组（p  < 0.05）。此外，基于析因设计的数据分析表明，AlCl ₃和ApoEε4之间存在相互作用（p  < 0.05）。

结论

Al和ApoEε4基因可引起SH-SY5Y细胞形态学改变，降低细胞活性，并有明显的细胞毒作用，增加tau的磷酸化水平，增加Aβ的沉积。在Al和ApoEε4基因同时存在的情况下，这两个因素相互作用并表现出协同效应。