The Importance of Thioredoxin-1 in Health and Disease

Abstract

Thioredoxin-1 (Trx-1) is a multifunctional protein ubiquitously found in the human body. Trx-1 plays an important role in various cellular functions such as maintenance of redox homeostasis, proliferation, and DNA synthesis, but also modulation of transcription factors and control of cell death. Thus, Trx-1 is one of the most important proteins for proper cell and organ function. Therefore, modulation of Trx gene expression or modulation of Trx activity by various mechanisms, including post-translational modifications or protein–protein interactions, could cause a transition from the physiological state of cells and organs to various pathologies such as cancer, and neurodegenerative and cardiovascular diseases. In this review, we not only discuss the current knowledge of Trx in health and disease, but also highlight its potential function as a biomarker.

Nuclear translocation of thioredoxin-1 promotes colorectal cancer development via modulation of the IL-6/STAT3 signaling axis through interaction with STAT3

“…Sustained activation of STAT3 in the nucleus is considered a hallmark of many human tumor types and leads to upregulation of a number of growth-promoting genes that contribute to tumor aggressiveness 16 , 36 . Recent studies have confirmed that intracellular Trx-1 is translocated to the nucleus in response to environmental stimuli, including oxidative stress 20 , 37 , 38 . Trx-1 is considered an anti-oxidant, anti-apoptotic effector, and redox regulator in signal transduction in response to H 2 O 2 stimulation 20 , 39 .…”

“…Recent studies have confirmed that intracellular Trx-1 is translocated to the nucleus in response to environmental stimuli, including oxidative stress 20 , 37 , 38 . Trx-1 is considered an anti-oxidant, anti-apoptotic effector, and redox regulator in signal transduction in response to H 2 O 2 stimulation 20 , 39 . Our results showed Trx-1 nuclear translocation to be induced by treatment with IL-6, and that translocation to be suppressed after knockdown of STAT3 or specific deactivation of STAT3 phosphorylation.…”

“…Thioredoxin-1 (Trx-1) is a small and ubiquitous protein with multiple functions including antioxidant and redox regulation, modulation of transcription factor activity, and regulation of apoptosis 18 - 20 . Trx-1 protein is predominantly located in the cytoplasm in humans, where it interacts with multiple proteins, including inhibiting apoptosis induction 21 .…”

Identification and validation of biomarkers in membranous nephropathy and pan-cancer analysis

“…TXN is indispensable for the normal functioning of both organs and tumors. It is strongly associated with various diseases, notably cancer, and ample evidence has been presented to underscore its significance in influencing the phenotype and prognosis of lung, gastrointestinal, and urological cancers ( 41 ). On the other hand, urinary TXN is regarded as a biomarker for diagnosing tubular redox dysregulation ( 42 ).…”

The Dual Roles of S-Nitrosylation of Proteins in Cancer: Molecular Mechanisms and Recent Advancements

“…Trx-1 induced activation of NOS3 and S-nitrosyation of CD95 leading to an increase of caspase-8 activity and caspase-3 activity [98] (Figure 8). This mechanism ultimately leads to reduced liver damage and promotes apoptosis of liver cancer cells [99].…”