科研之友
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摘要
Manganese (Mn) is an essential trace element. However, exposure to excessive Mn may cause neurodegenerative disorders called manganism. Accumulating evidence indicated that dysregulation of Wnt/beta-catenin signaling was tightly associated with the onset of neurodegenerative disorders. However, whether aberrant Wnt/beta-catenin signaling contributes to Mn-induced neurotoxicity remains unknown. The present study investigates the involvement of Wnt/beta-catenin signaling in Mn-induced neurotoxicity. Western blot and immunohistochemistry analyses showed a remarkable downregulation of p-Ser9-glycogen synthase kinase-3 beta (GSK-3 beta) and beta-catenin in rat striatum after Mn exposure. TUNEL assay revealed significant neuronal apoptosis following treatment with 25 mg/kg Mn. Immunofluorescent staining showed that beta-catenin was expressed predominantly in neurons, and colocalization of beta-catenin and active caspase-3 was observed after Mn exposure. Furthermore, Mn exposure resulted in PC12 cells apoptosis, which was accompanied by reduced levels of cellular beta-catenin and p-GSK-3 beta. Accordingly, the mRNA level of the prosurvival factor survivin, a downstream target gene of beta-catenin, was synchronously decreased. More importantly, blockage of GSK-3 beta activity with the GSK-3 beta inhibitor lithium chloride could attenuate Mn-induced downregulation of beta-catenin and survivin as well as neuronal apoptosis. Overall, the present study demonstrates that downregulation of Wnt/beta-catenin signaling pathway may be of vital importance in the neuropathological process of Mn-induced neurotoxicity.
- 出版日期2014-6
- 单位南通大学
