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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
发表期刊BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
ISSN1554-351X
文章类型期刊论文
卷号1830期号:8页码:4102-4116
产权排序1
摘要Background: 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.
关键词Formaldehyde Tau hyperphosphorylation GSK-3 beta Nuclear accumulation Protein polymerization Tauopathy
学科领域Medical Psychology,Cognitive Psychology
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收录类别SCI
语种英语
项目资助者673-Project [2012CB911004, 2010CB912303] ; Natural Scientific Foundation of China [NSFC 30970695] ; QCAS Biotechnology Fund [GJHZ1131]
项目简介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研究方向Biochemistry & Molecular Biology ; Biophysics
WOS类目Biochemistry & Molecular Biology ; Biophysics
WOS记录号WOS:000320896100010
WOS标题词Science & Technology ; Life Sciences & Biomedicine
关键词[WOS]GLYCOGEN-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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文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/10806
专题脑与认知科学国家重点实验室
通讯作者He, RQ (reprint author), Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, 15 Datun Rd, Beijing 100101, Peoples R China.
作者单位1.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
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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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