ABSTRACT
Aim To study the protection and possible mechanism of 5-hydroxy-1 H-indazole against 1-methyl-4-phenylpyridinium iodide ( MPP+)-induced SH-SY5 Y cell apoptosis. Methods An apoptotic model was es-tablished in human neuroblastoma SH-SY5 Y by MPP+in vitro. MTT analysis was used to evaluate the protec-tive effect of 5-hydroxy-1H-indazole. Immunochemistry and Hoechst33258 nuclear staining were used to ob-serve the neuroprotection and anti-apoptosis of 5-hy-droxy-1H-indazole. Western blot was used to detect the levels of P-tau ( Ser396 ) closely related to neuronal apoptosis and its upstream kinases:P-GSK-3β and CDK5 . Results MPP+ induced activation of GSK-3β, increase of activity of CDK5 , tau hyperphosphory-lation and neuronal cell apoptosis. However,5-hydrox-y-1 H-indazole reduced the activities of GSK-3β and CDK5,then decreased the level of tau hyperphosphory-lation and inhibited MPP+-induced SH-SY5 Y cells ap-optosis. Conclusions 5-hydroxy-1H-indazole could attenuate MPP+-induced SH-SY5 Y neuronal cell apop-tosis. Possible mechanism is that 5-hydroxy-1H-in-dazole inhibits GSK-3βand CDK5 two signal transduc-tion pathways to lower the level of tau phosphorylation, then plays a role of neuroprotection.
