Journal Article

Manganese Induces Tau Hyperphosphorylation through the Activation of ERK MAPK Pathway in PC12 Cells

Tongjian Cai, Honglei Che, Ting Yao, Yaoming Chen, Chuanshu Huang, Wenbin Zhang, Kejun Du, Jianbin Zhang, Yunxin Cao, Jingyuan Chen and Wenjing Luo

in Toxicological Sciences

Volume 119, issue 1, pages 169-177
Published in print January 2011 | ISSN: 1096-6080
Published online October 2010 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfq308
Manganese Induces Tau Hyperphosphorylation through the Activation of ERK MAPK Pathway in PC12 Cells

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Manganese has long been known to induce neurological degenerative disorders. Emerging evidence indicates that hyperphosphorylated tau is associated with neurodegenerative diseases, but whether such hyperphosphorylation plays a role in manganese-induced neurotoxicity remains unclear. To fill this gap, we investigated the effects of manganese on tau phosphorylation in PC12 cells. In our present research, treatment of cells with manganese increased the phosphorylation of tau at Ser199, Ser202, Ser396, and Ser404 as detected by Western blot. Moreover, this manganese-induced tau phosphorylation paralleled the activation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK). The mitogen-activated protein kinase kinase-1 (MEK1) inhibitor PD98059, which inhibits the activation of ERK MAPK, partially attenuated manganese-induced tau hyperphosphorylation and cytotoxicity. Moreover, the activation of ERK MAPK was involved in the activation of glycogen synthase kinase-3β (GSK-3β) kinase, which also contributed to the hyperphosphorylation of tau and the cytotoxicity in PC12 cells induced by manganese. Taken together, we found for the first time that the exposure to manganese can cause the hyperphosphorylation of tau, which may be connected with the activation of ERK MAPK.

Keywords: manganese; tau; PC12 cell; ERK MAPK; GSK-3β

Journal Article.  5118 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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