AcSDKP对抗β-淀粉样蛋白诱导细胞凋亡作用

The effects of AcSDKP on apoptosis induced by β-amyloid protein

目的:建立寡聚体Aβ1-42(Oligomeric Aβ1-42,oAβ1-42)诱导阿尔茨海默病(Alzheimer’s disease,AD)样细胞模型,探索N-乙酰-丝-天冬-赖-脯氨酸(AcSDKP)对抗β-淀粉样蛋白诱导细胞凋亡作用。方法:用oAβ1-42及AcSDKP处理SH-SY5Y细胞,采用MTT法检测细胞存活率、Western blotting检测BCL2和BAX蛋白表达变化、细胞色素c(Cyt c)释放量和NF-κB信号分子,以探究AcSDKP对细胞的保护作用。结果:用oAβ1-42处理SH-SY5Y细胞24 h后,MTT法检测显示:oAβ1-42对SH-SY5Y细胞毒性作用呈浓度依赖关系,大于2.5μmol oAβ1-42能明显降低细胞存活率,而5μmol oAβ1-42处理细胞24 h,细胞的活力呈现显著降低约50%;Western blotting检测表明AcSDKP使BAX的水平显著低于Aβ处理组,且在AcSDKP处理组,BCL2的水平较Aβ单独处理组显著升高;结果还显示:AcSDKP明显减少Cytc的释放量;同时观察到oAβ1-42促进了NF-κB表达,而AcSDKP能显著抑制NF-κB表达。结论:AcSDKP具有对抗oAβ1-42诱导的细胞凋亡作用,其可能机制是通过抑制NF-κB信号通路。

Objective To establish Alzheimer’s disease(AD)-like cellular model induced by Oligomeric Amyloid-beta1-42(oAβ1-42)and explore the effects of acetyl-Ser-Asp-Lys-Pro(AcSDKP)on apoptosis induced byβ-amyloid protein.Methods SH-SY5Y cells were treated with oAβ1-42 and AcSDKP.The viability of SH-SY5Y cells was examined,the expression of BCL2 and BAX protein,the release of cytochrome C(Cyt c)and the signal molecular NF-κB were assayed by Western blotting.The neuroprotection of AcSDKP was explored on the cells.Results SH-SY5Y cells were treated with oAβ1-42 for 24 hours,MTT assay showed that the toxicity of oAβ1-42 to SH-SY5Y cells was concentrationdependent,more than 2.5μmol oAβ1-42 could significantly decrease the viability of cells,while viability was decreased by about 50%after treatment with 5μmol of oAβ1-42 for 24h.Western blotting showed that the level of BAX in AcSDKP group was significantly lower than that in Aβtreatment group,and the level of BCL2 in AcSDKP treatment group was significantly higher than that in Aβtreatment group.The results also showed that AcSDKP significantly decreased the release of Cytc.At the same time,it was observed that oAβ1-42 promoted the expression of NF-κB,while AcSDKP could significantly inhibit the expression of NF-κB.Conclusion AcSDKP could inhibit apoptosis induced by oAβ1-42,which may be due to the inhibition of NF-κB signaling pathway.