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Thioredoxin 1 protects astrocytes from oxidative stress by maintaining peroxiredoxin activity.

Authors :
Wang M
Zhu K
Zhang L
Li L
Zhao J
Source :
Molecular medicine reports [Mol Med Rep] 2016 Mar; Vol. 13 (3), pp. 2864-70. Date of Electronic Publication: 2016 Feb 03.
Publication Year :
2016

Abstract

Previous studies have demonstrated that thioredoxin 1 (Trx1) exerts neuroprotective effects against cerebral ischemia/reperfusion injury caused by oxidative stress. While Trx1 is known to maintain the anti‑oxidant activity of 2‑Cys peroxiredoxins (Prdxs), the underlying mechanisms of its protective effects have remained to be elucidated, which was the aim of the present study. For this, an in vitro ischemic model of hypoxemia lasting for 4 h, followed by 24 h of reperfusion was used. Primary astrocytes from neonatal rats were pre‑treated with small interfering RNA targeting Trx1 prior to oxygen glucose deprivation/reperfusion (OGD/R). MTS and lactate dehydrogenase assays were performed to evaluate cell viability. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis were employed to assess the mRNA and protein expression levels of Prdx1‑4 and Prdx‑SO3. Furthermore, a dual luciferase reporter assay was used to assess the interaction between activator protein‑1 (AP‑1) and Trx1. The present study demonstrated that OGD/R decreased the cell viability and increased cellular damage, which was more marked following Trx1 knockdown. The expression of Prdx1‑4 and Prdx‑SO3 protein was higher in the cells subjected to OGD/R. Knockdown of Trx1 markedly decreased the levels of Prdx1‑4 but increased Prdx‑SO3 mRNA and protein levels. The results of the present study also suggested that AP‑1 directly activated the expression of Trx1. The present study demonstrated that Trx1 exerts its neuroprotective effects by preventing oxidative stress in astrocytes via maintaining Prdx expression.

Details

Language :
English
ISSN :
1791-3004
Volume :
13
Issue :
3
Database :
MEDLINE
Journal :
Molecular medicine reports
Publication Type :
Academic Journal
Accession number :
26846911
Full Text :
https://doi.org/10.3892/mmr.2016.4855