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Cells constantly face the challenge of managing oxidants. In aerobic organisms, oxygen (O2) is used for energy production, generating reactive oxygen species (ROS) as byproducts of enzymatic reactions. To protect against oxidative damage, cells possess an intricate system of redox scavengers and antioxidant enzymes, collectively forming the antioxidant defense system. This system maintains the redox equilibrium and enables the generation of localized oxidative signals that regulate essential cellular functions. One key component of this defense is the thioredoxin (Trx) system, which includes Trx, thioredoxin reductase (TrxR), and NADPH. The Trx system reverses oxidation of macromolecules and indirectly neutralizes ROS via peroxiredoxin (Prx). This dual function protects cells from damage accumulation and supports physiological cell signaling. However, the Trx system also shields tumors from oxidative damage, aiding their survival. Due to elevated ROS levels from their metabolism, tumors often rely on the Trx system. In addition, the Trx system regulates critical pathways such as proliferation and neoangiogenesis, which tumors exploit to enhance growth and optimize nutrient and oxygen supply. Consequently, the Trx system is a potential target for cancer therapy. The challenge lies in selectively targeting malignant cells without disrupting the redox equilibrium in healthy cells. The aim of this review article is threefold: first, to elucidate the function of the Trx system; second, to discuss the Trx system as a potential target for cancer therapies; and third, to present the possibilities for inhibiting key components of the Trx system, along with an overview of the latest clinical studies on these inhibitors. [ABSTRACT FROM AUTHOR]

Bacterial infections trigger a multifaceted interplay between inflammatory mediators and redox regulation. Recently, accumulating evidence has shown that redox signaling plays a significant role in immune initiation and subsequent immune cell functions. This review addresses the crucial role of the thioredoxin (Trx) system in the initiation of immune reactions and regulation of inflammatory responses during bacterial infections. Downstream signaling pathways in various immune cells involve thiol-dependent redox regulation, highlighting the pivotal roles of thiol redox systems in defense mechanisms. Conversely, the survival and virulence of pathogenic bacteria are enhanced by their ability to counteract oxidative stress and immune attacks. This is achieved through the reduction of oxidized proteins and the modulation of redox-sensitive signaling pathways, which are functions of the Trx system, thereby fortifying bacterial resistance. Moreover, some selenium/sulfur-containing compounds could potentially be developed into targeted therapeutic interventions for pathogenic bacteria. Taken together, the Trx system is a key player in redox regulation during bacterial infection, and contributes to host–pathogen interactions, offering valuable insights for future research and therapeutic development. [ABSTRACT FROM AUTHOR]

Climate change adversely affects the water and temperature conditions required for plant growth, leading to a decrease in yield. In high temperatures, oxidative stress causes cellular damage in plant cells, which is a negative factor for crop production. Thioredoxin (Trx) is a small redox protein containing a conserved WC(G/P)PC motif that catalyzes the exchange of disulfide bonds. It is known to play an important role in maintaining cellular redox homeostasis. Trx proteins are widely distributed across various subcellular locations, and they play a crucial role in responding to cellular stresses. In this study, seven CaTrxh-type genes present in pepper were identified and the CaTrxh-type family was classified into three subgroups. CaTrxh genes responded to heat stress. Moreover, subcellular locations of the CaTrxh family exhibited dynamic patterns in normal conditions, and we observed relocalizations in heat stress conditions. Each CaTrxh family protein member formed homo-/heteromeric protein complexes in BiFC assay. Unexpectedly, subgroup III CaTrxh9 and CaTrxh10 can recruit subgroup I and II CaTrxh proteins into the plasma membrane. Thus, the function of the CaTrxh-type family is expected to play a protective role in the cell in response to high-temperature stress via protein complex formations. CaTrxh may have potential applications in the development of crops with enhanced tolerance to oxidative stress. [ABSTRACT FROM AUTHOR]

The phytotoxic mechanisms of patulin (PAT) and penicillic acid (PA) have not been identified unambiguously. This study aims to clarify their effects on thioredoxins (Trxs). Aflatoxin B1 (AFB1), PAT and PA were isolated by solvent extraction and chromatographic techniques from the cultures of Aspergillus flavus Z2 (LC171449), Penicillium vulpinum CM1 and Aspergillus ochraceus EMCC516, respectively. The three mycotoxins showed phytotoxicity to the germination of maize seeds, which was manifested by inhibiting radicle and coleoptile emergence, in addition to their toxic effects on fresh weights and root and shoot lengths. The phytotoxicity of AFB1 and PAT was greater than that of PA. Due to the central roles exhibited by plant Trxs in cellular metabolic activities, they were tested as target proteins for PAT and PA using AFB1 as positive control. In vivo studies showed that the mycotoxins significantly reduced Trx activity measured in the roots and shoots of maize seedlings. PAT showed greater Trx-inhibiting activity than PA and AFB1. In vitro studies of the mycotoxins on Trx y1 (from Arabidopsis thaliana) and thioredoxin reductase (Tr, from rat liver) activities confirm the results of in vivo studies. The inactivation of Trx with PAT and PA was reduced in the presence of glutathione (GSH). Data obtained suggest that lactone mycotoxins are more highly reactive with simple low-molecular-weight thiols (like GSH) than with complex ones (like Trx). [ABSTRACT FROM AUTHOR]