TY - JOUR
T1 - Modulation of signaling mechanisms in the heart by thioredoxin 1
AU - Nagarajan, Narayani
AU - Oka, Shinichi
AU - Sadoshima, Junichi
N1 - Funding Information:
This work was supported in part by U.S. Public Health Service Grants HL67724, HL91469, HL102738, HL112330 and AG23039 (J.S.), and by the Leducq Foundation Transatlantic Network of Excellence (J.S.). N.N. has been supported by a Predoctoral Fellowship from the American Heart Association, Founders Affiliate 14PRE20480412.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/8
Y1 - 2017/8
N2 - 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.
AB - 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.
KW - Anti-oxidant
KW - Disulfide
KW - Ischemia/reperfusion
KW - Thioredoxin
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U2 - 10.1016/j.freeradbiomed.2016.12.020
DO - 10.1016/j.freeradbiomed.2016.12.020
M3 - Review article
C2 - 27993729
AN - SCOPUS:85008423148
SN - 0891-5849
VL - 109
SP - 125
EP - 131
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -