title: Selenoprotein S Reduces Endoplasmic Reticulum Stress-Induced Phosphorylation of Tau: Potential Role in Selenate Mitigation of Tau Pathology.
abstract: Previous studies demonstrated that selenium in the form of sodium selenate reduces neurofibrillary tangle formation in Alzheimer's disease models. Hyperphosphorylation of tau, which leads to formation of neurofibrillary tangles in Alzheimer's disease, is increased by endoplasmic reticulum (ER) stress. Selenoprotein S (SelS) is part of an ER membrane complex that removes misfolded proteins from the ER as a means to reduce ER stress. Selenate, as with other forms of selenium, will increase selenoprotein expression. We therefore proposed that increased SelS expression by selenate would contribute to the beneficial actions of selenate in Alzheimer's disease. SelS expression increased with ER stress and decreased under conditions of elevated glucose concentrations in the SH-SY5Y neuronal cell line. Reducing expression of SelS with siRNA promoted cell death in response to ER stress. Selenate increased SelS expression, which significantly correlated with decreased tau phosphorylation. Restricting SelS expression during ER stress conditions increased tau phosphorylation, and also promoted aggregation of phosphorylated tau in neurites and soma. In human postmortem brain, SelS expression coincided with neurofibrillary tangles, but not with amyloid-β plaques. These results indicate that selenate can alter phosphorylation of tau by increasing expression of SelS in Alzheimer's disease and potentially other neurodegenerative disorders.
authors: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai'i at Manoa, Honolulu, HI, USA.
authors: Rachel H L H
authors: RH
authors: Rueli
authors: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai'i at Manoa, Honolulu, HI, USA.
authors: Daniel J
authors: DJ
authors: Torres
authors: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai'i at Manoa, Honolulu, HI, USA.
authors: Andrea S T
authors: AS
authors: Dewing
authors: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai'i at Manoa, Honolulu, HI, USA.
authors: Arlene C
authors: AC
authors: Kiyohara
authors: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai'i at Manoa, Honolulu, HI, USA.
authors: Stephanie M
authors: SM
authors: Barayuga
authors: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai'i at Manoa, Honolulu, HI, USA.
authors: Miyoko T
authors: MT
authors: Bellinger
authors: Department of Pathology, John A. Burns School of Medicine, University of Hawai'i at Manoa, Honolulu, HI, USA.
authors: Jane H
authors: JH
authors: Uyehara-Lock
authors: Pacific Health Research and Education Institute, Honolulu, HI, USA.
authors: Lon R
authors: LR
authors: White
authors: Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra and Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors: Paula I
authors: PI
authors: Moreira
authors: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai'i at Manoa, Honolulu, HI, USA.
authors: Marla J
authors: MJ
authors: Berry
authors: UTSA Neurosciences Institute and Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA.
authors: George
authors: G
authors: Perry
authors: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai'i at Manoa, Honolulu, HI, USA.
authors: Frederick P
authors: FP
authors: Bellinger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007930:Leucine / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000494:pharmacology*; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011392:Proline / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051140:Selenoproteins / Q000235:genetics / Q000494:pharmacology*; D014162:Transfection; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C487710:SELENOS protein, human; D051140:Selenoproteins; D016875:tau Proteins; D011392:Proline; D007930:Leucine; D005947:Glucose
keywords: Alzheimer’s disease; endoplasmic reticulum stress; neurofibrillary tangle; selenium; selenoprotein; tau