Luteolin Reduces Zinc-Induced Tau Phosphorylation at Ser262/356 in an ROS-Dependent Manner in SH-SY5Y Cells

In brain, excess zinc alters the metabolism of amyloid precursor protein, leading to ??-amyloid protein deposition, one of the hallmarks of Alzheimer??s disease (AD) pathology. Recently, it has been reported that zinc accelerates in vitro tau fibrillization, another hallmark of AD. In the current study, we examined the effect of high-concentration zinc on tau phosphorylation in human neuroblastoma SH-SY5Y cells. We found that incubation of cells with zinc resulted in abnormal tau phosphorylation at Ser262/356. Moreover, the current study has investigated whether luteolin (Lu), a bioflavonoid, could decrease zinc-induced tau hyperphosphorylation and its underlying mechanisms. Using Western blot and protein phosphatase activity assay, activities of tau kinases and phosphatase were investigated. Our data suggest (1) that zinc induces tau hyperphosphorylation at Ser262/356 epitope and (2) that Lu efficiently attenuates zinc-induced tau hyperphosphorylation through not only its antioxidant action but also its regulation of the phosphorylation/dephosphorylation system.