Thioredoxin in the cardiovascular system
ABSTRACT The thioredoxin (TRX) system (TRX, TRX reductase, and NADPH) is a ubiquitous thiol oxidoreductase system that regulates cellular reduction/oxidation (redox) status. The impairment of cell redox state alters multiple cell pathways, which may contribute to the pathogenesis of cardiovascular disorders including hypertension, atherosclerosis, and heart failure. In this manuscript, we review the essential roles that TRX plays by limiting oxidative stress directly via antioxidant effects and indirectly by protein-protein interactions with key signaling molecules such as thioredoxin interacting protein (TXNIP). TRX and its endogenous regulators may represent important future targets to develop clinical therapies for diseases associated with oxidative stress.
- SourceAvailable from: PubMed Central
[Show abstract] [Hide abstract]
- "The Trx system, including Trx, Trx reductase, and NADPH, is a ubiquitous thiol oxidoreductase system that regulates cellular reduction/oxidation (redox) status . Trx reduces oxidized cysteine groups on proteins through an interaction with the redox-active center of Trx (Cys-Gly-Pro-Cys) to form a disulfide bond, which in turn can be reduced by TrxR and NADPH . "
ABSTRACT: Atherosclerosis is a chronic inflammation disease that is initiated by endothelial cell injury. Oxidized low-density lipoprotein (ox-LDL) is directly associated with chronic vascular inflammation. To understand whether thioredoxin1 (Trx1) participates in an antiinflammatory defense mechanism in atherosclerosis, we investigated the effect of Trx1 on the expression of two adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), in human umbilical vein endothelial cells (HUVECs). Thioredoxin1 and dominant-negative mutant thioredoxin1 (TD) were transiently overexpressed using adenovirus vector gene transfer. Our data showed that Trx1 overexpression suppressed ox-LDL-induced adhesion molecule expression in HUVECs. The overexpression of Trx1 promoted ox-LDL-induced Smad3 phosphorylation and nuclear translocation. A co-immunoprecipitation assay indicated that Smad3 continued to interact with Trx1 with or without ox-LDL stimulation. These results suggest that Trx1 inherently suppresses VCAM-1 and ICAM-1 expression in vascular endothelia and may prevent the initiation of atherosclerosis by attenuating adhesion molecule expression. The enhancement of Smad3 phosphorylation and nuclear expression appears to be primarily responsible for the Trx1-induced downregulation of adhesion molecules.PLoS ONE 09/2013; 8(9):e76226. DOI:10.1371/journal.pone.0076226 · 3.23 Impact Factor
[Show abstract] [Hide abstract]
- "However, pathological dysregulation of the redox balance could contribute to CVDs  . Cellular redox homeostasis is tightly regulated by the coordinated action of NADPH oxidases, the TRX system and glutathione (GSH) , among others. The TRX system and GSH are thiol reduction systems with a key role in the defense against excessive ROS production, as well as in the modulation of signaling processes such as inflammation, cellular proliferation, and apoptosis   . "
ABSTRACT: Cell stress proteins (CSPS) are a large and heterogeneous family of proteins, sharing two main characteristics: their levels and/or location are modified under stress and most of them can exert a chaperon function inside the cells. Nonetheless, they are also involved in the modulation of several mechanisms, both at the intracellular and the extracellular compartments. There are more than 100 proteins belonging to the CSPs family, among them the thioredoxin (TRX) system, which is the focus of the present paper. TRX system is composed of several proteins such as TRX and peroxiredoxin (PRDX), two thiol-containing enzymes that are key players in redox homeostasis due to their ability to scavenge potential harmful reactive oxygen species. In addition to their main role as antioxidants, recent data highlights their function in several processes such as cell signalling, immune inflammatory responses, or apoptosis, all of them key mechanisms involved in atherothrombosis. Moreover, since TRX and PRDX are present in the pathological vascular wall and can be secreted under prooxidative conditions to the circulation, several studies have addressed their role as diagnostic, prognostic, and therapeutic biomarkers of cardiovascular diseases (CVDs).Oxidative Medicine and Cellular Longevity 06/2012; 2012:232464. DOI:10.1155/2012/232464 · 3.36 Impact Factor
[Show abstract] [Hide abstract]
- "The induction of Hmox1 gene expression by APAP in this study suggested an increase of the antioxidant system to the APAP-triggered oxidative stress. Thioredoxin (Trx) system, involving Trx and Txnrd, is a ubiquitous thiol oxidoreductase system that regulates cellular reduction/oxidation (redox) status . Previous reports have suggested that Trx provides protection against ROS-mediated cardiotoxicity [15,16]. "
ABSTRACT: Hepatotoxicity of acetaminophen has been widely studied. However, the adverse effects on the heart have not been sufficiently evaluated. This study was performed to investigate cytotoxicity and alterations of gene expression in cultured cardiomyocytes (H(9)C(2) cells) after exposure to acetaminophen. H(9)C(2) cells were incubated in a 10 mM concentration of acetaminophen for the designated times (6, 12, and 24 hours), and cytotoxicity was determined by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Alteration of gene expression was observed by microarray analysis, and RT-PCR was performed for the three representative oxidative stress-related genes at 24 hours after treatment. It revealed that acetaminophen was toxic to cardiomyocytes, and numerous critical genes were affected. Induced genes included those associated with oxidative stress, DNA damage, and apoptosis. Repressed genes included those associated with cell proliferation, myocardial contraction, and cell shape control. These findings provide the evidences of acetaminophen-induced cytotoxicity and changes in gene expression in cultured cardiomyocytes of H(9)C(2) cells.04/2012; 27:e2012011. DOI:10.5620/eht.2012.27.e2012011