Formaldehyde induces hyperphosphorylation and polymerization of Tau protein both in vitro and in vivo

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	Formaldehyde induces hyperphosphorylation and polymerization of Tau protein both in vitro and in vivo
	Lu, Jing 1,3,4; Miao, Junye 1,3; Su, Tao 1,3; Liu, Ying 1; He, Rongqiao 1,2
刊名	BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
	2013
卷号	1830 期号:8 页码:4102-4116
关键词	Formaldehyde Tau hyperphosphorylation GSK-3 beta Nuclear accumulation Protein polymerization Tauopathy
ISSN号	1554-351X
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.
产权排序	1
英文摘要	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.
学科主题	Medical psychology,Cognitive psychology
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]	Biochemistry & Molecular Biology ; Biophysics
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
收录类别	SCI
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].
原文出处	http://ac.els-cdn.com/S0304416513001682/1-s2.0-S0304416513001682-main.pdf?_tid=92ae60d8-b27e-11e4-9f0a-00000aab0f6c&acdnat=1423721922_5e2696ec0fa35433802d4ab310b62e16
语种	英语
WOS记录号	WOS:000320896100010
内容类型	期刊论文
源URL	[http://ir.psych.ac.cn/handle/311026/10806]
专题	心理研究所_脑与认知科学国家重点实验室
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
推荐引用方式 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.(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.