Details

Autor(en) / Beteiligte

• Larrarte Lazaro, Eider

Titel

Transferencia génica intramuscular de proteínas desacoplantes (UCP1 y UCP2)

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2002

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• The primary energy drive for ATP synthesis is the mitochondrial proton gradient generated across the inner membrane when substrates are oxidized. However, some of the energy is lost in the form of heat as protons return through independent pathways being a significant contributor for energy expenditure. Uncoupling protein 1 (UCP1) is involved in this proton leak in brown adipose tissue. UCP2 is expressed in many tissues and organs, but its function is still controversial. We sought to evaluate the potential of UCP2 or UCP1 muscle direct gene transfer and the effect of these proteins on muscle mitochondrial activity, since muscle transfer of DNA could be a useful tool to express a number of genes implicated in thermogenesis regulation. Rats received an intramuscular injection of plasmid containing UCP1 or UCP2 cDNA in the right tibialis muscles, while left muscles were used as control. Ten days after DNA injection, muscle mitochondria were isolated and analyzed. UCP1 or UCP2 gene transfer resulted in muscle protein expression. Furthermore we demonstrated that UCP2 muscle gene transfer is associated with a lower mitochondrial membrane potential, suggesting the potential involvement of UCP2 in uncoupling respiration. Mitochondria expressing UCP1 showed increased oxygen consumption rates and decreased membrane potential when compared with control mitochondria. Our results revealed that UCP1 muscle gene transfer is associated with an induced mitochondrial proton leak, which could contribute to increase energy expenditure.