Thyroid-hormone effects on putative biochemical pathways involved in UCP3 activation in rat skeletal muscle mitochondria |
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Authors: | Silvestri E Moreno M Lombardi A Ragni M de Lange P Alexson S E H Lanni A Goglia F |
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Affiliation: | Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy. |
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Abstract: | In vitro, uncoupling protein 3 (UCP3)-mediated uncoupling requires cofactors [e.g., superoxides, coenzyme Q (CoQ) and fatty acids (FA)] or their derivatives, but it is not yet clear whether or how such activators interact with each other under given physiological or pathophysiological conditions. Since triiodothyronine (T3) stimulates lipid metabolism, UCP3 expression and mitochondrial uncoupling, we examined its effects on some biochemical pathways that may underlie UCP3-mediated uncoupling. T3-treated rats (Hyper) showed increased mitochondrial lipid-oxidation rates, increased expression and activity of enzymes involved in lipid handling and increased mitochondrial superoxide production and CoQ levels. Despite the higher mitochondrial superoxide production in Hyper, euthyroid and hyperthyroid mitochondria showed no differences in proton-conductance when FA were chelated by bovine serum albumin. However, mitochondria from Hyper showed a palmitoyl-carnitine-induced and GDP-inhibited increased proton-conductance in the presence of carboxyatractylate. We suggest that T3 stimulates the UCP3 activity in vivo by affecting the complex network of biochemical pathways underlying the UCP3 activation. |
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Keywords: | UCPs, uncoupling protein 1, 2, and 3 CoQ, coenzyme Q FA, fatty acid T3, triiodothyronine CAT, carboxyatractylate CPT, carnitine-palmitoyl-transferase system MTE-I, mitochondrial acyl-CoA thioesterase I HPLC, high-performance liquid-chromatography Eu, euthyroid rats Hyper, T3-treated rats ANT, adenine nucleotide translocase TPMP+, triphenylmethylphosphonium FCCP, carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone TT3, total T3 FT3, free T3 CoA, coenzyme A CoASH, coenzyme A reduced form |
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