Institutional Repository, Institute of Psychology, Chinese Academy of Sciences
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. | |
心理所单位排序 | 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 |
2013 | |
语种 | 英语 |
发表期刊 | BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS |
ISSN | 1554-351X |
卷号 | 1830期号:8页码:4102-4116 |
期刊论文类型 | 期刊论文 |
URL | 查看原文 |
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]. |
WOS关键词 | 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 |
WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics |
WOS类目 | Biochemistry & Molecular Biology ; Biophysics |
WOS记录号 | WOS:000320896100010 |
资助机构 | 673-Project [2012CB911004, 2010CB912303] ; Natural Scientific Foundation of China [NSFC 30970695] ; QCAS Biotechnology Fund [GJHZ1131] |
引用统计 | |
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 |
第一作者单位 | 脑与认知科学国家重点实验室 |
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,&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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