Etomoxir, Sodium 2-[6-(4-Chlorophenoxy)hexyl]oxirane-2-carboxylate, Up-Regulates Uncoupling Protein-3 mRNA Levels in Primary Culture of Rat Preadipocytes
| Autor: | Tomás Adzet, Juan C. Laguna, Manuel Vázquez, Rosa M. Sánchez, Marta Alegret, Àgatha Cabrero |
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| Rok vydání: | 1999 |
| Předmět: |
Biophysics
Oxidative phosphorylation Biology Biochemistry Ion Channels Mitochondrial Proteins chemistry.chemical_compound Adipocytes Animals Uncoupling Protein 3 Uncoupling protein Uncoupling Protein 2 RNA Messenger Enzyme Inhibitors Inner mitochondrial membrane Molecular Biology Beta oxidation Cells Cultured DNA Primers chemistry.chemical_classification Base Sequence Carnitine O-Palmitoyltransferase Stem Cells Membrane Transport Proteins Proteins Fatty acid Cell Biology Peroxisome Mitochondria Rats Cell biology chemistry Epoxy Compounds Carnitine palmitoyltransferase I Carrier Proteins Etomoxir |
| Zdroj: | Biochemical and Biophysical Research Communications. 263:87-93 |
| ISSN: | 0006-291X |
| DOI: | 10.1006/bbrc.1999.1332 |
| Popis: | Uncoupling proteins (UCPs) are mitochondrial membrane proton transporters that uncouple respiration from oxidative phosphorylation by dissipating the proton gradient across the membrane. Treatment of primary culture of rat preadipocytes for 24 h with 40 microM etomoxir, an irreversible inhibitor of carnitine palmitoyltransferase I (CPT-I), up-regulated UCP-3 mRNA levels (3. 6-fold induction), whereas changes in UCP-2 mRNA levels were not significant. As a consequence of increased UCP-3 expression, a fall in the mitochondrial membrane potential was detected by flow cytometry. Etomoxir treatment modified neither L-CPT-I (liver-type) nor PPARalpha mRNA levels in preadipocytes. In contrast, mRNA expression of acyl-CoA oxidase (ACO), the rate-limiting enzyme of peroxisomal fatty acid beta-oxidation, whose transcription is controlled by PPARalpha, was significantly induced (1.3-fold induction, P = 0.015). These findings suggest that the effects of etomoxir were mediated by PPARalpha. Since it has been reported that the intracellular accumulation of lipids following the inhibition of CPT-I by etomoxir leads to a PPARalpha-mediated metabolic response that increases the expression of genes involved in alternate fatty acid oxidation pathways, these results seem to implicate UCP-3 in this protective metabolic response. It remains to be studied whether reductions in the expression of UCP-3 could compromise this response, giving rise to lipotoxic effects on cells. |
| Databáze: | OpenAIRE |
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