Modulation of signaling mechanisms in the heart by thioredoxin 1

Article ID	Journal	Published Year	Pages	File Type
5501893	Free Radical Biology and Medicine	2017	29 Pages	PDF

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.

Keywords

ITRAQ Cys ICAT IκB ZDF SOD1 PGC-1α RIPC ASK1 Trx TrxR GSK CREB CDDP AP1 TXNIP TFBS PRX ATG4 Smyd1 Activator protein 1 (AP-1)Redd1 Inhibitor-κB Regulated in development and DNA damage responses 1 DTT AMPK NF-κB H2S CyP TAC NADPH HIF-1 TCA MSC HDAC NOx ROS Adenosine Triphosphate ATP Myocardial infarction angiotensin-II Akt tricarboxylic acid NADPH oxidase ischemia/reperfusion isobaric tags for relative and absolute quantitation Transgenic thioredoxin reductase transverse aortic constriction thioredoxin Ang-II Disulfide dithiothreitol transcription factor binding site Mesenchymal stem cells Hydrogen sulfide superoxide dismutase 1 Cysteine cyclophilin Anti-oxidant dominant negative hypoxia-inducible factor-1 nuclear factor-κB UTR یا untranslated regions untranslated region Zucker diabetic fatty rats isotope-coded affinity tag Nitric oxide nicotinamide adenine dinucleotide phosphate histone deacetylase cAMP response element binding protein protein kinase B adenosine monophosphate-activated protein kinase Peroxiredoxin Remote ischemic preconditioning apoptosis signal-regulating kinase glycogen synthase kinase Reactive oxygen species Peroxisome proliferator-activated receptor gamma coactivator-1α