Oxidative Stress Modifies the Levels and Phosphorylation State of Tau Protein in Human Fibroblasts.

Alejandro Ibáñez-Salazar,María E Jiménez-Capdeville,Sergio Rosales-Mendoza,Bernardo Bañuelos-Hernández,Elizabeth Monreal-Escalante,Ildefonso Rodríguez-Leyva,Erika Chi-Ahumada

doi:10.3389/fnins.2017.00495

Alejandro Ibáñez-Salazar, María E Jiménez-Capdeville + Show 5 more

Open Access

https://doi.org/10.3389/fnins.2017.00495

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Abstract

Since the tau protein is closely involved in the physiopathology of Alzheimer's disease (AD), studying its behavior in cellular models might lead to new insights on understanding this devastating disease at molecular levels. In the present study, primary cultures of human fibroblasts were established and used to determine the expression and localization of the tau protein in distinct phosphorylation states in both untransfected and tau gene-transfected cells subjected to oxidative stress. Higher immunopositivity to phospho-tau was observed in cell nuclei in response to oxidative stress, while the levels of total tau in the cytosol remained unchanged. These findings were observed in both untransfected cells and those transfected with the tau gene. The present work represents a useful model for studying the physiopathology of AD at the cellular level in terms of tau protein implications.

Highlights

Neurodegenerative disease is a general term for a range of conditions that primarily affect neurons in the brain, which is characterized by degeneration and/or progressive death of nerve cells leading to dementia and/or movement impairments (Seung-Jae et al, 2011)
First an anti-AT8 serum was obtained using a phosphorylated peptide, showing strong reactivity in histological sections of patients having Alzheimer’s disease (Rodríguez-Leyva et al, 2015) at a comparable level to that of the AT8 commercial antibody. This serum can be purified to serve as an alternative source of pathologic tau detection. This serum will be especially useful in experiments aiming at neutralizing prionic tau in fibroblast cultures that will require higher amounts of blocking tau antibodies in fibroblast cultures (Aguzzi et al, 2008; Woerman et al, 2016)
The behavior of tau upon oxidative stress was evaluated in fibroblast cultures, at experimental conditions where the viability of both control and tau-overexpressing fibroblasts was not compromised (Miyoshi et al, 2006; Loo and Halliwell, 2012)

Summary

Introduction

Neurodegenerative disease is a general term for a range of conditions that primarily affect neurons in the brain, which is characterized by degeneration and/or progressive death of nerve cells leading to dementia and/or movement impairments (Seung-Jae et al, 2011). One of the common characteristics of neurodegenerative diseases is the progressive accumulation of aggregates of specific proteins in the brain with a particular regional pattern for each disorder. As the diseases progress protein aggregates spread among brain cells, eliciting both microglial inflammatory responses and neuronal death (Muramatsu et al, 2008). Several neurodegenerative diseases share with AD tau misfolding and are recognized as taupathies. Recent research has focused on studying the factors leading to tau aggregation and apparent spreading in taupathies (Spillantini and Goedert, 2013)

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