脂联素通过激活PP2A减轻H_2O_2诱导的SH-SY5Y细胞损伤及tau蛋白过度磷酸化

Adiponectin attenuates H_2O_2-induced SH-SY5Y cell injury and tau hyperphosphorylation via activating PP2A

目的:观察脂联素(adiponectin)对H2O2诱导的人神经母细胞瘤SH-SY5Y细胞活力及tau蛋白磷酸化的影响并探讨其作用机制。方法:采用MTT法并观察细胞形态,检测脂联素对H2O2诱导的SH-SY5Y细胞活力损伤的影响;应用Western blotting观察脂联素对tau蛋白磷酸化及蛋白磷酸酶2A(protein phosphatase 2A,PP2A)和糖原合酶激酶3β(glycogen synthase kinase-3β,GSK-3β)活性的影响。结果:脂联素减轻了H2O2诱导的SH-SY5Y细胞损伤(P<0.01)。脂联素上调了H2O2诱导的SH-SY5Y细胞的PP2A活性,明显减轻此时tau的异常过度磷酸化(P<0.01)。PP2A抑制剂冈田酸阻断了脂联素的保护作用(P<0.01)。脂联素同时使H2O2诱导的SH-SY5Y细胞的GSK-3β磷酸化水平上升(P<0.01)。结论:脂联素减轻H2O2诱导的SH-SY5Y细胞损伤及tau蛋白异常过度磷酸化,其机制可能与激活PP2A并抑制GSK-3β信号途径有关。

AIM： To study the effects of adiponectin on H2O2-induced cell injury and tau hyperphosphorylation in human neuroblastoma SH-SY5 Y cells. METHODS： Cell viability was determined by MTT assay. H2O2-induced cell injury and morphological changes in the SH-SY5 Y cells with or without adiponectin treatment were observed. The level of tau phosphorylation as well as the activities of protein phosphatase 2A（ PP2A） and of glycogen synthase kinase-3β（ GSK-3β）were examined by Western blotting. RESULTS： Adiponectin significantly attenuated H2O2-induced cell injury（ P〈0. 01）. Adiponectin upregulated the activity of PP2 A and decreased phosphorylation levels of tau under the stimulation with H2O2（ P〈0. 01）. Okadaic acid,a specific inhibitor of PP2 A,blocked the protective effects of adiponectin（ P〈0. 01）. Adiponectin increased the phosphorylation level of GSK-3β at Ser9 site under H2O2stimulation（ P〈0. 01）. CONCLUSION： Adiponectin protects SH-SY5 Y cells against H2O2-induced cell injury and decreases tau hyperphosphorylation by activating PP2 A and inactivating GSK-3β.