PSYCH OpenIR  > 脑与认知科学国家重点实验室
Formaldehyde induces hyperphosphorylation and polymerization of Tau protein both in vitro and in vivo
Lu, Jing1,3,4; Miao, Junye1,3; Su, Tao1,3; Liu, Ying1; He, Rongqiao1,2; He, RQ (reprint author), Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, 15 Datun Rd, Beijing 100101, Peoples R China.
2013
Source PublicationBIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
ISSN1554-351X
Subtype期刊论文
Volume1830Issue:8Pages:4102-4116
Contribution Rank1
AbstractBackground: Chronic formaldehyde exposure leads to memory impairment and abnormal elevation of endogenous formaldehyde has been found in the brains of Alzheimer's disease (AD) patients. Hyperphosphorylated Tau protein with subsequent aggregates as neurofibrillary tangles (NFTs) is one of the typical pathological characteristics in AD brains. The mechanism underlying abnormally elevated concentrations of endogenous formaldehyde that induce Tau hyperphosphorylation is unknown. Methods: N2a cells and mice were treated with formaldehyde for different time points, then Western blotting and immunocytochemistry were utilized to determine the phosphorylation and polymerization of Tau protein. HPLC was used to detect the concentration of formaldehyde in cell media. Results: Under formaldehyde stress, Tau became hyperphosphorylated, not only in the cytoplasm, but also in the nucleus of neuroblastoma (N2a) cells, and mouse brains. Polymers of cellular phospho-Tau were also detected. Significant accumulation of glycogen synthase kinase-3 beta (GSK-3 beta) in the nucleus of N2a and mouse brain cells, and elevation of its phosphorylation at Y216, was observed under formaldehyde stress. Formaldehyde-induced Tau hyperphospholylation was blocked in the presence of LiCl and CT 99021, inhibitors of GSK-3 beta, and by RNAi interference. Conclusions: Formaldehyde, which may cause age-related memory loss, can act as a factor triggering Tau hyperphosphorylation via GSK-3 beta catalysis and induces polymerization of Tau. General significance: Investigation of formaldehyde-induced Tau hyperphosphorylation may provide novel insights into mechanisms underlying tauopathies. (c) 2013 Elsevier B.V. All rights reserved.
KeywordFormaldehyde Tau hyperphosphorylation GSK-3 beta Nuclear accumulation Protein polymerization Tauopathy
Subject AreaMedical Psychology,Cognitive Psychology
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Indexed BySCI
Language英语
Funding Organization673-Project [2012CB911004, 2010CB912303] ; Natural Scientific Foundation of China [NSFC 30970695] ; QCAS Biotechnology Fund [GJHZ1131]
Project Intro.This work was supported by the 673-Project [2012CB911004, 2010CB912303]; the Natural Scientific Foundation of China [NSFC 30970695] and the QCAS Biotechnology Fund [GJHZ1131].
WOS Research AreaBiochemistry & Molecular Biology ; Biophysics
WOS SubjectBiochemistry & Molecular Biology ; Biophysics
WOS IDWOS:000320896100010
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS KeywordGLYCOGEN-SYNTHASE KINASE-3-BETA ; CYCLIN-DEPENDENT KINASE-5 ; ALZHEIMERS-DISEASE ; POSTTRANSLATIONAL MODIFICATIONS ; NEUROFIBRILLARY TANGLES ; ENDOGENOUS FORMALDEHYDE ; ALDEHYDE DEHYDROGENASES ; ALCOHOL DEHYDROGENASES ; CEREBROSPINAL-FLUID ; TRANSGENIC ANIMALS
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Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/10806
Collection脑与认知科学国家重点实验室
Corresponding AuthorHe, RQ (reprint author), Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, 15 Datun Rd, Beijing 100101, Peoples R China.
Affiliation1.Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China
2.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia
Recommended Citation
GB/T 7714
Lu, Jing,Miao, Junye,Su, Tao,et al. Formaldehyde induces hyperphosphorylation and polymerization of Tau protein both in vitro and in vivo[J]. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS,2013,1830(8):4102-4116.
APA Lu, Jing,Miao, Junye,Su, Tao,Liu, Ying,He, Rongqiao,&He, RQ .(2013).Formaldehyde induces hyperphosphorylation and polymerization of Tau protein both in vitro and in vivo.BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS,1830(8),4102-4116.
MLA Lu, Jing,et al."Formaldehyde induces hyperphosphorylation and polymerization of Tau protein both in vitro and in vivo".BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS 1830.8(2013):4102-4116.
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