Thioredoxins (Trx) regulate redox signaling and are localized to different cellular compartments. Specific redox regulated pathways for adaptation of skeletal muscle to contractions are attenuated during aging, but little is known about the roles of Trx in regulating these pathways. This study investigated the susceptibility of Trx1 and Trx2 in skeletal muscle to oxidation and reduction in vitro and the effect of age in g and contractions on Trx1, Trx2, thioredoxin reductase (TrxR) 1 and 2 contents, nuclear and cytosolic Trx1 and mitochondrial Trx2 redox potentials in vivo. The proportions of cytosolic and nuclear Trx1 and mitochondrial Trx2 in the oxidized or reduced forms were analyzed using redox western blotting. In myotubes, the mean redox potentials were nuclear Trx1: 251mV, cytosolic Trx1: 242mV, mitochondrial Trx2: 346mV, data supporting the occurrence of differing redox potentials between cell compartments. Exogenous treatment of myoblasts and myotubes with hydrogen peroxide or dithiothreitol modified glutathione redox status and nuclear and cytosolic Trx1, but mitochondrial Trx2 was unchanged. Tibialis anterior muscles from young 2 and old mice were exposed to isometric muscle contractions in vivo. Aging increased muscle contents of Trx1, Trx2 and TrxR2, but neither ageing nor endogenous ROS generated during contractions modified Trx redox potentials, although oxidation of glutathione and other thiols occurred. We conclude that glutathione redox couples in skeletal muscle are more susceptible to oxidation than Trx, that Trx proteins are upregulated during aging, but do not appear to modulate redox regulated adaptations to contractions that fail during ageing.
In vitro susceptibility of thioredoxins and glutathione to redox modification and aging-related changes in skeletal muscle
Dimauro I;Caporossi D;
2012-01-01
Abstract
Thioredoxins (Trx) regulate redox signaling and are localized to different cellular compartments. Specific redox regulated pathways for adaptation of skeletal muscle to contractions are attenuated during aging, but little is known about the roles of Trx in regulating these pathways. This study investigated the susceptibility of Trx1 and Trx2 in skeletal muscle to oxidation and reduction in vitro and the effect of age in g and contractions on Trx1, Trx2, thioredoxin reductase (TrxR) 1 and 2 contents, nuclear and cytosolic Trx1 and mitochondrial Trx2 redox potentials in vivo. The proportions of cytosolic and nuclear Trx1 and mitochondrial Trx2 in the oxidized or reduced forms were analyzed using redox western blotting. In myotubes, the mean redox potentials were nuclear Trx1: 251mV, cytosolic Trx1: 242mV, mitochondrial Trx2: 346mV, data supporting the occurrence of differing redox potentials between cell compartments. Exogenous treatment of myoblasts and myotubes with hydrogen peroxide or dithiothreitol modified glutathione redox status and nuclear and cytosolic Trx1, but mitochondrial Trx2 was unchanged. Tibialis anterior muscles from young 2 and old mice were exposed to isometric muscle contractions in vivo. Aging increased muscle contents of Trx1, Trx2 and TrxR2, but neither ageing nor endogenous ROS generated during contractions modified Trx redox potentials, although oxidation of glutathione and other thiols occurred. We conclude that glutathione redox couples in skeletal muscle are more susceptible to oxidation than Trx, that Trx proteins are upregulated during aging, but do not appear to modulate redox regulated adaptations to contractions that fail during ageing.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
