细胞外基质金属蛋白酶诱导因子与阿尔茨海默病γ-分泌酶的相关性研究

Relationship between extracellular matrix metalloproteinase inducer and γ-secretase in Alzheimer's disease

摘要:

目的 探讨细胞外基质金属蛋白酶诱导因子(CD147)与阿尔茨海默病γ-分泌酶的相关性。方法 CD147 cDNA转染人神经母细胞瘤,并通过遗传霉素G418筛选CD147超表达细胞。超表达细胞设为实验组,正常细胞设为对照组,Western Blot检测两组CD147含量,Elisa分析两组Aβ40和Aβ42含量。结果 实验组和对照组CD147含量分别为(40.23±0.20)μg/μL和(27.98±0.12)μg/μL,实验组显著高于对照组(t=90.97, P<0.05)。实验组和对照组Aβ40与Aβ42总含量分别为(141.05±2.13)pg/mL和(323.41±2.78)pg/mL,实验组显著低于对照组(t=90.19,P<0.05)。结论 随着CD147含量的增加,Aβ的生成减少,而γ-分泌酶是生成Aβ的限速酶,可知γ-分泌酶随着CD147含量的增加而呈负增长,提示CD147对γ-分泌酶的活性起着负调节作用。

Abstract:

Objective To investigate the relationship between extracellular matrix metalloproteinase inducer (CD147) and γ-secretase in Alzheimer's disease.Methods CD147 cDNA was transfected into human neuroblastoma cells, and cells with overexpression of CD147 were selected by neomycin G418. CD147 overexpression cells and normal cells were set as experimental group and control group, respectively. The expression of CD147 protein in the two groups were determined by Western blot, and the content of amyloid β protein (Aβ) 40 and Aβ42 in the two groups was analyzed by enzyme-linked immunosorbent assay.Results The expression of CD147 protein was significantly higher in the experimental group than in the control group (40.23±0.20 vs. 27.98±0.12 μg/μl; t=90.97, P<0.05). Moreover, the total content of Aβ40 and Aβ42 was significantly lower in the experimental group than in the control group (141.05±2.13 vs. 323.41±2.78 pg/ml; t=90.19, P<0.05).Conclusions The synthesis of Aβ is reduced with increasing CD147 content. Given that γ-secretase is the rate-limiting enzyme in Aβ synthesis, the level of γ-secretase should be reduced with increasing CD147 content, indicating that CD147 is a negative regulator of γ-secretase activity.