title: C-Reactive Protein Induces Tau Hyperphosphorylation via GSK3β Signaling Pathway in SH-SY5Y Cells.
abstract: Amyloid plaques and neurofibrillary tangles are the key pathological features of Alzheimer's disease (AD). Studies have shown that C-reactive protein (CRP) increases during inflammatory reactions and, therefore, has been associated with AD. However, there is no published report relating the impact of CRP to the regulation of tau phosphorylation. In the present study, we investigated the effects of CRP on the phosphorylation of tau protein in SH-SY5Y cells. Treatment of cells with CRP (5, 10, 20 μg/ml) resulted in neurotoxicity and apoptosis, as was observed by MTT assay and Hoechst staining, respectively. Western blot analysis showed that CRP, in a time- and concentration-dependent manner, induced the phosphorylation of tau at Ser202 and ser396 in SH-SY5Y cells. Phosphorylation of Akt (Ser473) and GSK3β (Ser9) were decreased by CRP treatment, whereas phosphorylation of ERK and p38 were not affected. Pharmacological inhibition of GSK3β reversed the effects induced by CRP, viz., cytotoxicity, apoptosis, and tau phosphorylation. Herein, we present a novel mechanism of cell death following CRP insult, which activates tau hyperphosphorylation by regulating GSK3β activity. CRP could potentially be used as an important pathological factor for the therapeutic intervention of AD.
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Haibiao
authors.initials: H
authors.lastname: Guo
authors.forename: Haitao
authors.initials: H
authors.lastname: Wang
authors.forename: Canmao
authors.initials: C
authors.lastname: Wang
authors.forename: Yufang
authors.initials: Y
authors.lastname: Cheng
authors.forename: Zhengqiang
authors.initials: Z
authors.lastname: Zou
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Li
authors.forename: Jingang
authors.initials: J
authors.lastname: Wu
authors.forename: Jiangping
authors.initials: J
authors.lastname: Xu
mesh_terms: D017209:Apoptosis; D002097:C-Reactive Protein / Q000494:pharmacology*; D045744:Cell Line, Tumor; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D002097:C-Reactive Protein; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3