Glutathione system in Wolfram syndrome 1‑deficient mice

Porosk,Rando; Kilk,Kalle; Mahlapuu,Riina; Terasmaa,Anton; Soomets,Ursel

doi:10.3892/mmr.2017.7419

Glutathione system in Wolfram syndrome 1‑deficient mice

Authors:
- Rando Porosk
- Kalle Kilk
- Riina Mahlapuu
- Anton Terasmaa
- Ursel Soomets
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Affiliations: Department of Biochemistry, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia, Centre of Excellence for Genomics and Translational Medicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia
Published online on: August 31, 2017 https://doi.org/10.3892/mmr.2017.7419
Pages: 7092-7097

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Abstract

Wolfram syndrome 1 (WS) is a rare neurodegenerative disease that is caused by mutations in the Wolfram syndrome 1 (WFS1) gene, which encodes the endoplasmic reticulum (ER) glycoprotein wolframin. The pathophysiology of WS is ER stress, which is generally considered to induce oxidative stress. As WS has a well‑defined monogenetic origin and a model for chronic ER stress, the present study aimed to characterize how glutathione (GSH), a major intracellular antioxidant, was related to the disease and its progression. The concentration of GSH and the activities of reduction/oxidation system enzymes GSH peroxidase and GSH reductase were measured in Wfs1‑deficient mice. The GSH content was lower in most of the studied tissues, and the activities of antioxidative enzymes varied between the heart, kidneys and liver tissues. The results indicated that GSH may be needed for ER stress control; however, chronic ER stress from the genetic syndrome eventually depletes the cellular GSH pool and leads to increased oxidative stress.

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