出版社：American Society for Biochemistry and Molecular Biology
摘要：Peroxisome proliferator-activated receptor (PPAR) is a transcriptionalregulator of the expression of mitochondrial thioesterase I(MTE-I) and uncoupling protein 3 (UCP3), which are induced inthe heart at the mRNA level in response to diabetes. Littleis known about the regulation of protein expression of MTE-Iand UCP3 or about MTE-I activity; thus, we investigated theeffects of diabetes and treatment with a PPAR agonist on theseparameters. Rats were either made diabetic with streptozotocin(55 mg/kg ip) and maintained for 10–14 days or treatedwith the PPAR agonist fenofibrate (300 mg/kg/day) for 4 weeks.MTE-I and UCP3 protein expression, MTE-1 activity, palmitateexport, and oxidative phosphorylation were measured in isolatedcardiac mitochondria. Diabetes and fenofibrate increased cardiacMTE-I mRNA, protein, and activity (4-fold compared with controls).This increase in activity was matched by a 6-fold increase inpalmitate export in fenofibrate-treated animals, despite therebeing no effect in either group on UCP3 protein expression.Both diabetes and fenofibrate caused significant decreases instate III respiration of isolated mitochondria with pyruvate+ malate as the substrate, but only diabetes reduced state IIIrates with palmitoylcarnitine. Both diabetes and specific PPARactivation increased MTE-I protein, activity, and palmitateexport in the heart, with little effect on UCP3 protein expression.Supplementary key words cardiac • fatty acids • lipotoxicity
Abbreviations: IFM, interfibrillar mitochondria; MTE-I, mitochondrial thioesterase I; P/O, ADP-to-oxygen ratio; PPAR, peroxisome proliferator-activated receptor ; RCR, respiratory control ratio; SSM, subsarcolemmal mitochondria; UCP3, uncoupling protein 3
(PPAR
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 PPAR
