The regulation of thioredoxin system in chronic stress-induced depression
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Date
2018-10-18
Authors
Zhou, Hong
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Abstract
Chronic stress is a key contributor to depression. It can cause oxidative stress which is also increased in depression. Thioredoxin (Trx) is a ubiquitous reductase that can reverse protein cystine oxidative modification, including sulfenylation and nitrosylation, and inhibit the apoptosis signal-regulating kinase 1 (ASK1) pathway. Thioredoxin-interacting protein (Txnip) is an endogenous Trx inhibitor.
The chronic unpredictable stress (CUS) animal model is wildly used to mimic human depression. We found that mice exposed to CUS displayed decreased exploratory, increased anhedonic and increased despair depressive-like behaviours. Although Trx protein levels didn’t change, Txnip protein levels were significantly increased in hippocampus, frontal cortex and nucleus accumbens of CUS mice. Further investigation demonstrated an increase in protein sulfenylation, nitrosylation and ASK1 phosphorylation in CUS mice hippocampus and frontal cortex.
These findings suggest that chronic stress may upregulate Txnip protein levels, subsequently inhibiting Trx activity and enhancing protein cysteine oxidative modification and the ASK1 pathway.
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Keywords
Thioredoxin, Thioredoxin-interacting protein, Chronic unpredictable stress, Sulfenylation
Citation
Zhou, H., Tan, H., Letourneau, L., & Wang, J. F. (2019). Increased thioredoxin-interacting protein in brain of mice exposed to chronic stress. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 88, 320-326.