1.030001 太原,山西医科大学基础医学院:病理教研室
2.030001 太原,山西医科大学基础医学院:基础医学研究中心
Received:14 March 2022,
Revised:2022-05-06,
Published:15 September 2022
移动端阅览
Ning WANG, Xiuya ZHOU, Xinghong HE, et al. STX17 improves Aβ31-35 induced death of hippocampal neurons in mice[J]. Journal of Army Medical University, 2022, 44(17): 1712-1719.
Ning WANG, Xiuya ZHOU, Xinghong HE, et al. STX17 improves Aβ31-35 induced death of hippocampal neurons in mice[J]. Journal of Army Medical University, 2022, 44(17): 1712-1719. DOI: 10.16016/j.2097-0927.202203123.
目的
2
探究突触融合蛋白17(syntaxin17,STX17)在Aβ诱导的小鼠海马神经细胞死亡中的作用。
方法
2
基于WGCNA方法选取与阿尔茨海默病显著相关的基因,与自噬基因库和SNARE家族基因取交集筛选关键基因;C57BL/6小鼠海马组织中注射浓度为1 g/L的Aβ31-35和使用终浓度为5 μmol/L Aβ31-35处理HT22海马神经细胞,采用Western Blot检测STX17、LC3Ⅱ、P62的蛋白表达情况;CCK-8法检测Aβ31-35处理的HT22海马神经细胞存活率;慢病毒介导HT22海马神经细胞STX17过表达后,Western blot检测Aβ31-35处理后LC3Ⅱ、P62的蛋白表达情况。
结果
2
与阿尔茨海默病显著相关的Salmon和Black模块分别与自噬基因库和SNARE亚家族取交集获取关键基因STX17。与对照组比较,经Aβ31-35处理后,HT22细胞细胞存活率[(81.81±11.65)%
]
明显下降(
P
<
0.05),小鼠海马组织和HT22细胞中STX17蛋白表达均显著降低(
P
<
0.05),LC3Ⅱ和P62蛋白表达均显著升高(
P
<
0.05);慢病毒介导HT22海马神经细胞STX17过表达后,显著逆转Aβ31-35诱导的LC3Ⅱ、P62的蛋白表达上调(
P
<
0.05),并改善Aβ31-35诱导的HT22海马神经细胞存活率下降[(101.91±13.81)%
vs
(79.21±8.75)%,
P
<
0.05
]
。
结论
2
STX17通过促进自噬来改善Aβ诱导的小鼠海马神经细胞死亡。
Objective
2
To explore the role of STX17 protein in Aβ-induced death of mouse hippocampal neuronal cells.
Methods
2
Based on Weighted correlation network analysis (WGCNA)
the modules significantly related to Alzheimer's disease (AD) were selected
and key genes were screened for cross-fertilization with autophagy gene bank and SNARE family genes. Aβ31-35 at a concentration of 1 g/L was used to inject the C57BL/6 mouse hippocampal tissue
and HT22 hippocampal neuronal cells were treated with 5 μmol/L Aβ31-35. Then the protein expression of STX17
LC3 Ⅱ and P62 was detected by Western blotting. The survival rate of the HT22 hippocampal neuronal cells treated by using Aβ31-35 was detected by CCK-8 assay. Protein expression of LC3Ⅱ and P62 were determined by Western blotting after overexpression STX17 in HT22 hippocampal neuronal cells.
Results
2
The Salmon and Black modules significantly associated with AD crossed with autophagic gene pool and SNARE subfamily intersection STX17
respectively. Under the action of Aβ31-35 mouse hippocampal tissue and mouse HT22 hippocampal neuronal cells
and the survival rate of HT22 cells [(81.81±11.65)%
vs
(100.00±12.89)%
P
<
0.05
]
were decreased significantly
and the expression of STX17 was significantly reduced in both tissue and cells (
P
<
0.05). The expression of tissue LC3Ⅱ and P62 proteins were significantly elevated in the tissue (
P
<
0.05)
and in the cells (
P
<
0.05). After lentivirus-mediated overexpression of STX17 in HT22 hippocampal neuronal cells
the protein expression upregulation of LC3II and P62 induced by Aβ31-35 was significantly reversed
and the survival rate was improved in Aβ31-35-induced HT22 hippocampal neuronal cells [(101.91±13.81)%
vs
(79.21±8.75)%
P
<
0.05
]
.
Conclusion
2
STX17 improves Aβ-induced death of mouse hippocampal neuronal cells by promoting autophagy.
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