Thioredoxin-Interacting Protein: Pathophysiology and Emerging Pharmacotherapeutics in Cardiovascular Disease and Diabetes

Chong, Cher-Rin, Chan, Wai Ping A., Nguyen, Thanh H., Liu, Saifei, Procter, Nathan E. K., Ngo, Doan T., Sverdlov, Aaron L., Chirkov, Yuliy Y. and Horowitz, John D. (2014) Thioredoxin-Interacting Protein: Pathophysiology and Emerging Pharmacotherapeutics in Cardiovascular Disease and Diabetes. Cardiovascular Drugs and Therapy, 28 (4). pp. 347-360. ISSN 0920-3206

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Abstract

The thioredoxin system, which consists of thioredoxin (Trx), nicotinamide adenine dinucleotide phosphate (NADPH) and thioredoxin reductase (TrxR), has emerged as a major anti-oxidant involved in the maintenance of cellular physiology and survival. Dysregulation in this system has been associated with metabolic, cardiovascular, and malignant disorders. Thioredoxin-interacting protein (TXNIP), also known as vitamin D-upregulated protein or thioredoxin-binding-protein-2, functions as a physiological inhibitor of Trx, and pathological suppression of Trx by TXNIP has been demonstrated in diabetes and cardiovascular diseases. Furthermore, TXNIP effects are partially Trx-independent; these include direct activation of inflammation and inhibition of glucose uptake. Many of the effects of TXNIP are initiated by its dissociation from intra-nuclear binding with Trx or other SH-containing proteins: these effects include its migration to cytoplasm, modulating stress responses in mitochondria and endoplasmic reticulum, and also potentially activating apoptotic pathways. TXNIP also interacts with the nitric oxide (NO) signaling system, with apparent suppression of NO effect. TXNIP production is modulated by redox stress, glucose levels, hypoxia and several inflammatory activators. In recent studies, it has been shown that therapeutic agents including insulin, metformin, angiotensin converting enzyme inhibitors and calcium channel blockers reduce TXNIP expression, although it is uncertain to what extent TXNIP suppression contributes to their clinical efficacy. This review addresses the role of TXNIP in health and in cardiovascular and metabolic disorders. Finally, the potential advantages (and disadvantages) of pharmacological suppression of TXNIP in cardiovascular disease and diabetes are summarized

Item Type: Article
Uncontrolled Keywords: thioredoxin-interacting protein,thioredoxin,diabetes,cardiovascular diseases,oxidative stress,inflammation,nitric oxide,therapeutics
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: LivePure Connector
Date Deposited: 19 Nov 2018 13:30
Last Modified: 22 Apr 2020 07:14
URI: https://ueaeprints.uea.ac.uk/id/eprint/68944
DOI: 10.1007/s10557-014-6538-5

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