U18666A对星形胶质瘤U373细胞APP代谢及Aβ生成的影响

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Abstract Objective To investigate the effect of cholesterol transport inhibitor U18666A (UA) on amyloid precursor protein (APP) metabolism and β-amyloid protein (Aβ) generation in U373 cells of astroglioma. Methods U373 cells were treated with UA at the dose of zero, one, three and five μg/mL for 24 h or 5 μg/mL UA for different times (0, 12, 24, 48 h). The expressions of APP and its metabolites α-CTF and β-CTF were detected using Western blot. The cellular levels of Aβ1-40 were measured with enzyme linked immunosorbent assay and the activity of β-secretase was determined by fluorescence assay. Results The expression levels of APP, α-CTF and β-CTF, and Aβ1-40 in 5 μg/mL UA group were higher than those in 0 μg/mL UA group, and the differences were statistically significant (P < 0.05 or P < 0.01). The expression levels of APP, α-CTF and β-CTF, and Aβ1-40 in co-cultured 24 h and 48 h groups were significantly higher than those in co-cultured 0 h group, and the differences were highly statistically significant (all P < 0.01). The activity of β-secretase in 5 μg/mL UA group was significantly higher than that in the control group (P < 0.01). Conclusion UA enhances APP expression and metabolism by increasing β-secretase activity, promotes Aβ1-40 generation, accelerates the pathological process of Alzheimer′s disease.

Key words： Cholesterol U18666A U373 cell Amyloid precursor protein β-amyloid protein

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	YANG Hongyan1▲ DU Xiaohui1 BAO Ya′nan1 HAN Yunfeng2 Tian Hua1▲

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YANG Hongyan1▲ DU Xiaohui1 BAO Ya′nan1 HAN Yunfeng2 Tian Hua1▲. Effect of U18666A on APP metabolism and Aβ generation in U373 cells of astroglioma[J]. 中国医药导报, 2020, 17(22): 4-7.

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http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2020/V17/I22/4

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