The Regulation of Mitochondrial Fatty Acid Oxidation and Hepatic Gene Expression by Catecholamine
| Autor: | Paul S. Brady, Linda J. Brady, Roderick A. Barke |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
medicine.medical_specialty
Transcription Genetic Dopamine Mitochondria Liver Biology chemistry.chemical_compound Catecholamines Liver Neoplasms Experimental Dobutamine Internal medicine Gene expression Ketogenesis Tumor Cells Cultured medicine Animals RNA Messenger Carnitine Cells Cultured Methionine Carnitine O-Palmitoyltransferase Fatty Acids Liver Neoplasms Blotting Northern Endocrinology Gene Expression Regulation Liver chemistry Dopamine receptor Catecholamine Surgery Oxidation-Reduction medicine.drug |
| Zdroj: | Journal of Surgical Research. 54:95-101 |
| ISSN: | 0022-4804 |
| Popis: | We hypothesized that dopamine or dobutamine may alter hepatic mitochondrial fatty acid oxidation secondary to an effect on hepatic gene expression. We investigated the effect of dopamine or dobutamine on hepatic fat oxidation and gene transcription by studying the enzyme carnitine palmitoyltransferase (CPT), the rate-limiting step in hepatic mitochondrial long-chain fat oxidation. We incubated either H4IIE rat hepatoma cells or rat hepatocytes in primary cell culture with either dopamine (1, 0.1, 0.01 microgram/ml), dobutamine (1, 0.1, 0.01 microgram/ml), or vehicle control for 1, 2, 3, or 4 hr. We investigated the effect on (1) CPT mRNA (Northern or dot blotting) and the possible regulatory mechanism by incubating dopamine (0.1 microgram/ml) or dobutamine (0.1 microgram/ml) with propranolol or phentolamine, (2) CPT translation (CPT [35S]methionine incorporation), and (3) hepatic mitochondrial fatty acid oxidation ([1-14C]-palmitate oxidation to acid-soluble products). We conclude that (1) dopamine or dobutamine increases both hepatic CPT mRNA and CPT protein translation, (2) the effect on CPT mRNA is mediated by the beta-receptor, (3) the increase in hepatic mitochondrial fat oxidation induced by dopamine or dobutamine may be, in part, secondary to increased CPT transcription and translation, and (4) the significant difference in hepatic fat oxidation induced by dopamine as compared with that by dobutamine is secondary to factors other than transcriptional or translational mechanisms. We speculate that dopamine treatment in the critically ill may increase hepatic mitochondrial fatty acid oxidation and ketogenesis and that this increase in beta-oxidation may be, in part, secondary to increased CPT gene expression. |
| Databáze: | OpenAIRE |
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