The Effects Of Aluminum And ApoE ε4on The Level Of Tau Phosphorylation And Expression Of Aβ In SH-SY5Y Cells

ObjectiveTo study the effects of aluminum and ApoE ε4on the level of tau phosphorylation and expression of Aβ in SH-SY5Y cells, and discuss the interaction between aluminum and ApoE ε4allele.MethodsThe selected SH-SY5Y cells were exposed to AICl3and transfected with ApoE ε4allele respectively, and divided into seven groups, including the blank control group, the low-dose group of200μM AICl3, the middle dose group of400μM AICl3, the high-dose group of800μM AICl3, empty plasmid group, ApoE ε4transfected group,400μM AICl3with ApoE ε4transfected group. Cell viability was assayed by CCK-8and expression of total protein and AP-40was detected with ELISA Kit after AICl3exposure or ApoE ε4transfection; factorial designing was performed to analyze interaction between AICl3and ApoE ε4.Results1. Observed under microscopy, as the aluminum concentration rose, the number of alive cells decreased, and synapses of the cells retracted. The viability of cells exposed to200μM AlC13,400μM AICl3and800μM AICl3is significantly lower than that of controls; ELISA results showed that the expressions of total tau, tau-181, tau-231, tau-262, tau-396and Aβ in200μM AlCl3,400μM AICl3and800μM AICl3exposed cells were significantly higher than those of controls.2. After the ApoE ε4transfection, the SH-SY5Y cell tended to be round in shape, easily disintegrated, and die; the viability of cells transfected with ApoE ε4is significantly lower than that of controls; ELISA results showed that the expressions of total tau protein, tau-181, tau-231, tau-262, tau-396and Aβ in ApoE ε4transfected cells were significantly higher than those of controls.3. The cells exposed to AICl3independently, and transfected with ApoE ε4combinedly, both appeared a morphology of cell loss, while the number of alive cells in AICl3plus ApoE ε4group was less than those treated with independent factor, either AICl3, or ApoE ε4. CCK-8analysis results showed lower cell viability than the blank control group; ELISA results showed that the expression of total tau, tau-181, tau-231, tau-262, tau-396and Aβ-40in the cells treated with AICl3plus ApoE ε4were significantly higher than those in other groups (P<0.05). Based on the factorial design, a significant interaction exists, and there is a synergistic effect between AICl3and ApoE ε4(P<0.05).Conclusion1. Aluminum (an environmental causal factor for Alzheimer’s disease) and the ApoE ε4allele (a genetic causal factor for Alzheimer’s disease) both led to SH-SY5Y cell morphology changes, decreased cell viability and showed significant cytotoxicity.2. Aluminum and ApoE ε4allele could both increase levels of tau phosphorylation and Aβ deposition.3. There was a synergistic interaction between aluminum and ApoE ε4allele in inducing SH-SY5Y cell death, tau phosphorylation and deposition.