Extranuclear or nongenomic effects of thyroid hormone are unaffected by the inhibitors of protein synthesis, and their time course cannot be explained by the interaction of the hormone molecule with nuclear receptors. Their site of action has been localized at the plasma membrane and identified very recently. In particular thyroid hormone has been reported to activate, by both genomic and non genomic mechanism, the Ca2+-ATPase, an ion pump that removes calcium from the cytosol and stores it in the sarcoplasmic reticulum. The decrease in intracellular Ca2+ generated during the systole leads to cardiac muscle relaxation. Given to all these important effects on the cardiovascular system, T3 can be also envisaged as a potent novel therapeutic agent as a inotropic drug. The Na/H exchanger, activated in L-6 myoblasts by the thyroid hormone through both genomic and nongenomic mechanism, is a ubiquitous plasma membrane integral protein exchanging extracellular Na+ with cytoplasmic H+ ions according to the concentration gradient; it does not require energy supply, but depends on the Na+/K+-ATPase. The transduction of the hormone signal in this nongenomic response requires tyrosine kinase-dependent phospholipase C activation and two different signaling pathways: 1) mobilization of intracellular calcium, through activation of IP3-receptors and without contributions from extracellular calcium or ryanodine receptors; 2) protein phosphorylation involving protein kinase C and mitogen-activated protein kinase (MAPK; ERK1/2), likely interfaces between genomic and nongenomic effects. The extranuclear actions should be taken into account when considering appropriate therapeutic intervention based on thyroid hormone both for their possible reinforcement of the nuclear responses and for their fast time onset, that might be of clinical relevance particularly for the cardiovascular system. Department of Biology, University of Rome “Roma Tre”, Viale Extranuclear or nongenomic effects of thyroid hormone are unaffected by the inhibitors of protein synthesis, and their time course cannot be explained by the interaction of the hormone molecule with nuclear receptors. Their site of action has been localized at the plasma membrane and identified very recently. In particular thyroid hormone has been reported to activate, by both genomic and non genomic mechanism, the Ca2+-ATPase, an ion pump that removes calcium from the cytosol and stores it in the sarcoplasmic reticulum. The decrease in intracellular Ca2+ generated during the systole leads to cardiac muscle relaxation. Given to all these important effects on the cardiovascular system, T3 can be also envisaged as a potent novel therapeutic agent as a inotropic drug. The Na/H exchanger, activated in L-6 myoblasts by the thyroid hormone through both genomic and nongenomic mechanism, is a ubiquitous plasma membrane integral protein exchanging extracellular Na+ with cytoplasmic H+ ions according to the concentration gradient; it does not require energy supply, but depends on the Na+/K+-ATPase. The transduction of the hormone signal in this nongenomic response requires tyrosine kinase-dependent phospholipase C activation and two different signaling pathways: 1) mobilization of intracellular calcium, through activation of IP3-receptors and without contributions from extracellular calcium or ryanodine receptors; 2) protein phosphorylation involving protein kinase C and mitogen-activated protein kinase (MAPK; ERK1/2),
Incerpi, S. (2005). NONGENOMIC EFFECTS OF THYROID HORMONES ON ION TRANSPORT. In non disponibile (pp.non disponibile). non disponibile : non disponibile.
NONGENOMIC EFFECTS OF THYROID HORMONES ON ION TRANSPORT
INCERPI, Sandra
2005-01-01
Abstract
Extranuclear or nongenomic effects of thyroid hormone are unaffected by the inhibitors of protein synthesis, and their time course cannot be explained by the interaction of the hormone molecule with nuclear receptors. Their site of action has been localized at the plasma membrane and identified very recently. In particular thyroid hormone has been reported to activate, by both genomic and non genomic mechanism, the Ca2+-ATPase, an ion pump that removes calcium from the cytosol and stores it in the sarcoplasmic reticulum. The decrease in intracellular Ca2+ generated during the systole leads to cardiac muscle relaxation. Given to all these important effects on the cardiovascular system, T3 can be also envisaged as a potent novel therapeutic agent as a inotropic drug. The Na/H exchanger, activated in L-6 myoblasts by the thyroid hormone through both genomic and nongenomic mechanism, is a ubiquitous plasma membrane integral protein exchanging extracellular Na+ with cytoplasmic H+ ions according to the concentration gradient; it does not require energy supply, but depends on the Na+/K+-ATPase. The transduction of the hormone signal in this nongenomic response requires tyrosine kinase-dependent phospholipase C activation and two different signaling pathways: 1) mobilization of intracellular calcium, through activation of IP3-receptors and without contributions from extracellular calcium or ryanodine receptors; 2) protein phosphorylation involving protein kinase C and mitogen-activated protein kinase (MAPK; ERK1/2), likely interfaces between genomic and nongenomic effects. The extranuclear actions should be taken into account when considering appropriate therapeutic intervention based on thyroid hormone both for their possible reinforcement of the nuclear responses and for their fast time onset, that might be of clinical relevance particularly for the cardiovascular system. Department of Biology, University of Rome “Roma Tre”, Viale Extranuclear or nongenomic effects of thyroid hormone are unaffected by the inhibitors of protein synthesis, and their time course cannot be explained by the interaction of the hormone molecule with nuclear receptors. Their site of action has been localized at the plasma membrane and identified very recently. In particular thyroid hormone has been reported to activate, by both genomic and non genomic mechanism, the Ca2+-ATPase, an ion pump that removes calcium from the cytosol and stores it in the sarcoplasmic reticulum. The decrease in intracellular Ca2+ generated during the systole leads to cardiac muscle relaxation. Given to all these important effects on the cardiovascular system, T3 can be also envisaged as a potent novel therapeutic agent as a inotropic drug. The Na/H exchanger, activated in L-6 myoblasts by the thyroid hormone through both genomic and nongenomic mechanism, is a ubiquitous plasma membrane integral protein exchanging extracellular Na+ with cytoplasmic H+ ions according to the concentration gradient; it does not require energy supply, but depends on the Na+/K+-ATPase. The transduction of the hormone signal in this nongenomic response requires tyrosine kinase-dependent phospholipase C activation and two different signaling pathways: 1) mobilization of intracellular calcium, through activation of IP3-receptors and without contributions from extracellular calcium or ryanodine receptors; 2) protein phosphorylation involving protein kinase C and mitogen-activated protein kinase (MAPK; ERK1/2),I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
