Thyroid-hormone effects on putative biochemical pathways involved in UCP3 activation in rat skeletal muscle mitochondria.
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.
Silvestri
E
E
Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi del Sannio, Via Port'Arsa 11, 82100 Benevento, Italy.
Moreno
M
M
Lombardi
A
A
Ragni
M
M
de Lange
P
P
Alexson
S E H
SE
Lanni
A
A
Goglia
F
F
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006980:Hyperthyroidism / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects; D007473:Ion Channels; D008564:Membrane Potentials / Q000187:drug effects; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010170:Palmitoyl-CoA Hydrolase / Q000235:genetics / Q000378:metabolism; D010172:Palmitoylcarnitine / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D014451:Ubiquinone / Q000378:metabolism; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; D014284:Triiodothyronine; D013481:Superoxides; D014451:Ubiquinone; D010172:Palmitoylcarnitine; D002334:Carnitine O-Palmitoyltransferase; D010170:Palmitoyl-CoA Hydrolase