Induction of uncoupling protein 3 gene expression in skeletal muscle of preterm newborns.
Prematurity is associated with delayed postnatal activation of mitochondrial oxidative phosphorylation and impaired switch from glycolytic to oxidative metabolism. Fatty acids (FA), which represent a major energy substrate in mature muscle cells, are engaged in the postnatal activation of genes of energy metabolism and lipid oxidation. To understand the mechanism activating mitochondria in human newborns, expression of the genes for mitochondrial uncoupling proteins (UCP) was characterized in autopsy samples of skeletal (n = 28) and cardiac (n = 13) muscles of preterm neonates, who mostly died during the first postnatal month, and two aborted fetuses. Transcripts levels for UCP2, UCP3, and also for genes engaged in the transport of FA between cytoplasm and mitochondria were measured using real-time reverse transcriptase PCR. In accordance with studies in mice, our results document postnatal induction of UCP3 gene expression in skeletal muscle, involvement of nutritional FA in the induction, and a role of UCP3 in mitochondrial FA oxidation. They suggest impaired postnatal activation of UCP3 gene in neonates delivered before approximately 26 wk of gestation. Mean levels of the UCP3 transcript in skeletal muscle were by two orders of magnitude higher than in the heart. In contrast to UCP3, the UCP2 gene was active in fetuses, and its expression was not affected by nutrition. Our results support a role of UCP3 in postnatal activation of lipid oxidation in skeletal muscle and suggest the involvement of UCP3 in the delayed activation of mitochondrial energy conversion in very immature preterm neonates.
Brauner
Petr
P
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Kopecký
Pavel
P
Flachs
Pavel
P
Ruffer
Josef
J
Sebron
Václav
V
Plavka
Richard
R
Vítková
Ivana
I
Vorlícek
Jaroslav
J
Kopecký
Jan
J
D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005333:Fetus / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005865:Gestational Age; D006321:Heart / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010085:Oxidative Phosphorylation; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; C000604390:Ucp2 protein, mouse; C000604393:Ucp3 protein, mouse; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3