title: Hyperosmotic Stress Induces Tau Proteolysis by Caspase-3 Activation in SH-SY5Y Cells.
abstract: Tau is a microtubule-associated protein implicated in the pathogenesis of Alzheimer's disease and other related tauopathies. In this subset of neurodegenerative disorders, Tau auto-assembles into insoluble fibrils that accumulate in neurons as paired helical filaments (PHFs), promoting cellular dysfunction and cytotoxic effects. Growing evidence suggests that abnormal post-translational regulation, mainly hyperphosphorylation and aberrant cleavage, drives Tau to this pathological state. In this work we show that sorbitol-induced hyperosmotic stress promotes Tau proteolysis in SH-SY5Y neuroblastoma cells. The appearance of cleaved Tau was preceded by the activation of μ-calpain, the proteasome system and caspase-3. Tau proteolysis was completely prevented by caspase-3 inhibition but unaffected by neither the proteasome system nor μ-calpain activity blockade. Concomitantly, hyperosmotic stress induced apoptosis in SH-SY5Y cells, which was efficiently avoided by the inhibition of caspase-3 activity. Altogether, our results provide the first evidence that Tau protein is susceptible to caspase-3 proteolysis under hyperosmotic stress and suggest a positive relationship between Tau proteolysis and apoptosis in SH-SY5Y cells. J. Cell. Biochem. 117: 2781-2790, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Faculty of Veterinary Sciences, Department of Biochemistry, Molecular Biology and Genetics, University of Extremadura, Cáceres, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Olivera-Santa Catalina
authors.affiliation: Faculty of Veterinary Sciences, Department of Biochemistry, Molecular Biology and Genetics, University of Extremadura, Cáceres, Spain.
authors.forename: Montaña
authors.initials: M
authors.lastname: Caballero-Bermejo
authors.affiliation: Faculty of Veterinary Sciences, Department of Biochemistry, Molecular Biology and Genetics, University of Extremadura, Cáceres, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Argent
authors.affiliation: Faculty of Veterinary Sciences, Department of Biochemistry, Molecular Biology and Genetics, University of Extremadura, Cáceres, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Alonso
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Cuenda
authors.affiliation: Faculty of Veterinary Sciences, Department of Biochemistry, Molecular Biology and Genetics, University of Extremadura, Cáceres, Spain. mjlorenzo@unex.es.
authors.forename: María J
authors.initials: MJ
authors.lastname: Lorenzo
authors.affiliation: Faculty of Sciences, Department of Biochemistry, Molecular Biology and Genetics, University of Extremadura, Badajoz, Spain. pacenten@unex.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Centeno
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism*; D049109:Cell Proliferation; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D009997:Osmotic Pressure; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; C505407:CASP3 protein, human; D053148:Caspase 3; D046988:Proteasome Endopeptidase Complex
keywords: APOPTOSIS; CASPASE-3; HYPEROSMOTIC STRESS; TAU PROTEOLYSIS