title: Modulation of signaling mechanisms in the heart by thioredoxin 1.
abstract: Myocardial ischemia/reperfusion and heart failure are the major cardiac conditions in which an imbalance between oxidative stress and anti-oxidant mechanisms is observed. The myocardium has endogenous reducing mechanisms, including the thioredoxin (Trx) and glutathione systems, that act to scavenge reactive oxygen species (ROS) and reduce oxidized proteins. The Trx system consists of Trx, Trx reductase (TrxR), and an electron donor, NADPH, where Trx is maintained in a reduced state in the presence of TrxR and NADPH. Trx1, a major isoform of Trx, is abundantly expressed in the heart and exerts its oxidoreductase activity through conserved Cys32 and Cys35, reducing oxidized proteins through thiol disulfide exchange reactions. In this review, we will focus on molecular targets of Trx1 in the heart, including transcription factors, microRNAs, histone deactylases, and protein kinases. We will then discuss how Trx1 regulates the functions of its targets, thereby affecting the extent of myocardial injury caused by myocardial ischemia/reperfusion and the progression of heart failure.
authors.affiliation: Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, 185 South Orange Ave, MSB G609, Newark, NJ 07103, USA.
authors.forename: Narayani
authors.initials: N
authors.lastname: Nagarajan
authors.affiliation: Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, 185 South Orange Ave, MSB G609, Newark, NJ 07103, USA.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.affiliation: Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, 185 South Orange Ave, MSB G609, Newark, NJ 07103, USA. Electronic address: sadoshju@njms.rutgers.edu.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sadoshima
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D054481:Thioredoxin Reductase 1 / Q000235:genetics / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D013879:Thioredoxins; D009249:NADP; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; D055372:AMP-Activated Protein Kinases; C400300:HDAC4 protein, human; D006655:Histone Deacetylases
keywords: Anti-oxidant; Disulfide; Ischemia/reperfusion; Thioredoxin