Hypoxia aggravates Aβl-42-induced toxicity in human neuroblastoma cells through PAK1/LIMK1/cofilin pathway
10.3760/cma.j.issn.0254-9026.2019.04.023
- VernacularTitle:缺氧加重淀粉样β蛋白对神经细胞毒性作用的通路探讨
- Author:
Qing YUAN
1
;
Min TANG
;
Qiuyun TU
Author Information
1. 中南大学湘雅三医院老年科
- Keywords:
Alzheimer disease;
Amyloid beta-protein;
Anoxia
- From:
Chinese Journal of Geriatrics
2019;38(4):444-448
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the pathways by which hypoxia aggravates the neurotoxic effects of amyloid-beta protein (Aβ) on neurons.Methods Human neuroblastoma cells (SH-SY5Y cells) were cultured in vitro,and were divided into four groups:the control group,Aβ intervention group,hypoxia group,Aβ intervention plus hypoxia group.Quantitative real time polymerase chain reaction(qRT-PCR) was adopted to detect the mRNA expression levels of p21-activated kinase 1 (PAK1),LIM kinase 1 protein (LIMK1)and cofilin.Western blot was used to measure the protein levels of PAK1,LIMK1,phosphate-LIMK1 (P-LIMK1),cofilin and phosphate-cofilin (P-cofilin).Results After Aβ treatment,the activity of SH-SY5Y cells was decreased.Compared with the control group,the protein levels of PAK1,LIMK1,P-LIMK1,P-cofilin,and the mRNA expression levels of PAK1 and LIMK1 were decreased(all P＜0.05),but the protein and mRNA expression of cofilin had no significant changes after 24 h of treatment with 10μmol/L Aβ.Compared with the Aβ intervention group,the protein levels of PAK 1,LIMK1,P-LIMK 1 and P-cofilin were decreased (all P ＜ 0.05),and the mRNA expression levels of PAK1 and LIMK1 were decreased(both P＜0.05),but the protein and mRNA expression of cofilin had no significant changes after 24 h of treatment of SH-SY5Y cells with 10 μmol/L Aβ plus 2％ oxygen.Conclusions Aβ may reduce P-LIMK1 expression by inhibiting the activity of PAK1,thereby reducing the P-cofilin,increasing the formation of dephosphorylated cofilin,leading to neural cells damage,and hypoxia aggravates the neurotoxicity of Aβ through this pathway.
