Diabetes or peroxisome proliferator-activated receptor α agonist increases mitochondrial thioesterase I activity in heart
| Autor: | Kristen L. King, Martin E. Young, Janos Kerner, Hazel Huang, Karen M. O'Shea, Stefan E.H. Alexson, Charles L. Hoppel, William C. Stanley |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | Journal of Lipid Research, Vol 48, Iss 7, Pp 1511-1517 (2007) |
| Druh dokumentu: | article |
| ISSN: | 0022-2275 21214778 |
| DOI: | 10.1194/jlr.M600364-JLR200 |
| Popis: | Peroxisome proliferator-activated receptor α (PPARα) is a transcriptional regulator of the expression of mitochondrial thioesterase I (MTE-I) and uncoupling protein 3 (UCP3), which are induced in the heart at the mRNA level in response to diabetes. Little is known about the regulation of protein expression of MTE-I and UCP3 or about MTE-I activity; thus, we investigated the effects of diabetes and treatment with a PPARα agonist on these parameters. Rats were either made diabetic with streptozotocin (55 mg/kg ip) and maintained for 10–14 days or treated with the PPARα agonist fenofibrate (300 mg/kg/day) for 4 weeks. MTE-I and UCP3 protein expression, MTE-1 activity, palmitate export, and oxidative phosphorylation were measured in isolated cardiac mitochondria. Diabetes and fenofibrate increased cardiac MTE-I mRNA, protein, and activity (∼4-fold compared with controls). This increase in activity was matched by a 6-fold increase in palmitate export in fenofibrate-treated animals, despite there being no effect in either group on UCP3 protein expression. Both diabetes and fenofibrate caused significant decreases in state III respiration of isolated mitochondria with pyruvate + malate as the substrate, but only diabetes reduced state III rates with palmitoylcarnitine. Both diabetes and specific PPARα activation increased MTE-I protein, activity, and palmitate export in the heart, with little effect on UCP3 protein expression. |
| Databáze: | Directory of Open Access Journals |
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