Cardiomyocyte-specific Txnip C247S mutation improves left ventricular functional reserve in streptozotocin-induced diabetic mice
Nobuhiro Mukai, Yoshinobu Nakayama, Syed Amir Abdali, Jun Yoshioka
Abstract
Thioredoxin-interacting protein (Txnip) has been of great interest as a molecular mechanism to mediate diabetic organ damage. Here, we provide novel evidence that a single mutation of Txnip confers a defense mechanism against myocardial oxidative stress in streptozotocin-induced diabetic mice. The results demonstrate the importance of Txnip as a cysteine-containing redox protein that regulates antioxidant thioredoxin via disulfide bond-switching mechanism and identify the cysteine in Txnip as a therapeutic target for diabetic cardiomyopathy.
Topics & Concepts
TXNIPThioredoxin-Interacting ProteinDiabetic cardiomyopathyStreptozotocinOxidative stressThioredoxinMechanism (biology)Diabetes mellitusCysteineAntioxidantChemistryCell biologyInternal medicineMedicineEndocrinologyCardiomyopathyBiologyBiochemistryHeart failureEnzymeEpistemologyPhilosophyRedox biology and oxidative stressNitric Oxide and Endothelin EffectsElectron Spin Resonance Studies