title: SIL1 Rescued Bip Elevation-Related Tau Hyperphosphorylation in ER Stress.
abstract: Endoplasmic reticulum (ER) stress has been indicated in the early stage of Alzheimer's disease (AD), in which tau hyperphosphorylation is one major pathological alteration. The elevation of binding immunoglobulin protein (Bip), an important ER chaperon, was reported in AD brain. It is important to study the roles of ER-related chaperons in tau hyperphosphorylation. In this research, increased Bip was found in the brains of the AD model mice (Tg2576) compared to the age-matched control mice. Meanwhile, deficiency of SIL1, an important co-chaperon of Bip, was observed in brains of Tg2576 mice and in ER stress both in vivo and in vitro. Then, we transfected Bip-EGFP plasmid into HEK293 cells stably expressing the longest human tau (HEK293/tau) or N2a cells and found that increased Bip induced tau hyperphosphorylation via activating glycogen synthase kinase-3β (GSK-3β), an important tau kinase, and increased the association with tau and GSK-3β. When we overexpressed SIL1 in Bip-transfected HEK293/tau cells and thapsigargin-treated HEK293/tau cells, significantly reduced tau hyperphosphorylation and GSK-3β activation were observed. These results suggested the important roles of ER-related chaperons, Bip and SIL1, in AD-like tau hyperphosphorylation.
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College; Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Institute of Brain Science, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.|2nd Hospital of Shijiazhuang, Shijiazhuang, 050051, China.
authors.forename: Zan-Chao
authors.initials: ZC
authors.lastname: Liu
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College; Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Institute of Brain Science, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chu
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College; Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Institute of Brain Science, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.|Hubei University of Traditional Chinese Medicine, Wuhan, 430061, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College; Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Institute of Brain Science, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College; Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Institute of Brain Science, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Lin-Na
authors.initials: LN
authors.lastname: Ning
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College; Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Institute of Brain Science, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.|Medical School, Hubei University for Nationalities, Enshi, 445000, China.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Luo
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College; Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Institute of Brain Science, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.|Hubei University of Traditional Chinese Medicine, Wuhan, 430061, China.
authors.forename: Shu-Sheng
authors.initials: SS
authors.lastname: Yang
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College; Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Institute of Brain Science, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College; Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Institute of Brain Science, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College; Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Institute of Brain Science, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Na
authors.initials: N
authors.lastname: Qu
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College; Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Institute of Brain Science, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College; Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Institute of Brain Science, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China. wangjz@mails.tjmu.edu.cn.
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College; Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Institute of Brain Science, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China. tianq@hust.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D057809:HEK293 Cells; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D019284:Thapsigargin / Q000494:pharmacology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D020662:Guanine Nucleotide Exchange Factors; D006360:Heat-Shock Proteins; D007211:Indoles; D008301:Maleimides; C417521:SB 216763; C000594797:SIL1 protein, mouse; D016875:tau Proteins; D019284:Thapsigargin; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: Alzheimer’s disease; Bip; GSK-3β; SIL1; Tau