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.

Hyperosmotic Stress Initiates AMPK-Independent Autophagy and AMPK- and Autophagy-Independent Depletion of Thioredoxin 1 and Glyoxalase 2 in HT22 Nerve Cells

“…Dehydration naturally occurs in humans and other animals for a number of reasons, including in the context of ageing and neurodegenerative diseases [4, 6, 7]. Of note, hyperosmotic stress clearly activates autophagy in nerve cells as previously reported in several studies using other types of cells [9–12].…”

“…Alzheimer's disease patients present an impaired response to fluid restriction, even in a mild overnight fluid restriction paradigm [5]. Increased tau phosphorylation and production of beta amyloid precursor proteins were also found in neuronal cells exposed to hyperosmotic stress, leading to altered cleavage of amyloid precursor protein, increasing beta amyloid peptides [6, 7]. Despite the enormous importance of understanding the homeostatic mechanisms underlying the response of nerve cells to osmotic stress, this topic has been underrepresented in the literature.…”

Sorbitol Destroyed Intestinal Microfold Cells (M Cells) Development through Inhibition of PDE4-Mediated RANKL Expression

“…In addition, the polyol pathway is necessary for ChREBP nuclear localization in hepatocytes and glucose tolerance in mice, and long-term uptake of sorbitol could induce a significant change in the composition of the gut microbiome [38]. The further work showed that sorbitol could induce an upregulation of Aquaporins 7 expression in a time-dependent manner [39] and apoptosis [40,41]. What is more, sorbitol was found to be able to relay gutfat body immunological communication (GFIC) by activation of metalloprotease 2, which further cleaved PGRP-LC to The classical second messenger cAMP pathway has been confirmed to be essential for a variety of physiological functions, including mitochondrial biology, lipid metabolism, ischemia, and inflammation [42].…”

Different Chronic Stress Paradigms Converge on Endogenous TDP43 Cleavage and Aggregation

“…References report recent usage of each stressor to human SH-SY5Y neuroblastoma cells Stressor Effect Acute Treatment Chronic Treatment References Serum Deprivation (SD) Lack of growth factors; Reduced nutrition / 1%. 72 h [ 32 ] Sodium Arsenite (Ars) Oxidative stress; Mitochondrial disruption 0.5 mM 1 h 20 µM 72 h [ 33 ] D-Sorbitol (Sorb) Hyperosmotic stress; Small molecules leakage 1.2 M 2 h 120 mM 72 h [ 34 ] Paraquat (PQ) Oxydative stress; ROS production 2 mM O.N 0.2 mM 72 h [ 35 ] …”