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The role of the thioredoxin/thioredoxin reductase system in the metabolic syndrome: towards a possible prognostic marker?

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Abstract

Mammalian thioredoxin reductase (TrxR) is a selenoprotein with three existing isoenzymes (TrxR1, TrxR2, and TrxR3), which is found primarily intracellularly but also in extracellular fluids. The main substrate thioredoxin (Trx) is similarly found (as Trx1 and Trx2) in various intracellular compartments, in blood plasma, and is the cell’s major disulfide reductase. Thioredoxin reductase is necessary as a NADPH-dependent reducing agent in biochemical reactions involving Trx. Genetic and environmental factors like selenium status influence the activity of TrxR. Research shows that the Trx/TrxR system plays a significant role in the physiology of the adipose tissue, in carbohydrate metabolism, insulin production and sensitivity, blood pressure regulation, inflammation, chemotactic activity of macrophages, and atherogenesis. Based on recent research, it has been reported that the modulation of the Trx/TrxR system may be considered as a new target in the management of the metabolic syndrome, insulin resistance, and type 2 diabetes, as well as in the treatment of hypertension and atherosclerosis. In this review evidence about a possible role of this system as a marker of the metabolic syndrome is reported.

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Abbreviations

HIV:

Human immunodeficiency virus

NADPH:

Nicotinamide adenine dinucleotide phosphate

PPAR-γ:

Peroxisome-proliferator-activated receptor-gamma

Se:

Selenium

Trx:

Thioredoxin

TrxR:

Thioredoxin reductase

TXNRD:

Thioredoxin reductase

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Acknowledgements

This paper was financially supported by the Ministry of Education and Science of the Russian Federation on the program to improve the competitiveness of Peoples’ Friendship University of Russia (RUDN University) among the world’s leading research and education centers in 2016–2020.

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Tinkov, A.A., Bjørklund, G., Skalny, A.V. et al. The role of the thioredoxin/thioredoxin reductase system in the metabolic syndrome: towards a possible prognostic marker?. Cell. Mol. Life Sci. 75, 1567–1586 (2018). https://doi.org/10.1007/s00018-018-2745-8

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  • DOI: https://doi.org/10.1007/s00018-018-2745-8

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