Modulation of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene by oxygen in rat hepatocyte cultures. Evidence for a heme protein as oxygen sensor
| Autor: | Helga Schmidt, Irmelin Probst, Thomas Kietzmann, Kurt Jungermann |
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| Rok vydání: | 1992 |
| Předmět: |
Male
medicine.medical_specialty Hemeprotein Cell Survival Partial Pressure Biophysics Biology Biochemistry Glucagon Gene Expression Regulation Enzymologic Ornithine decarboxylase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Structural Biology Lactate dehydrogenase Internal medicine Genetics medicine Phosphoenolpyruvate carboxykinase gene Animals RNA Messenger Rats Wistar Molecular Biology Cells Cultured 030304 developmental biology chemistry.chemical_classification 0303 health sciences Heme protein L-Lactate Dehydrogenase Cell Biology Cobalt Rats Oxygen Kinetics medicine.anatomical_structure Endocrinology Enzyme Hepatic oxygen sensing chemistry Liver Cell culture 030220 oncology & carcinogenesis Hepatocyte Phosphoenolpyruvate Carboxykinase (GTP) Phosphoenolpyruvate carboxykinase Metabolic zonation |
| Zdroj: | FEBS letters. 311(3) |
| ISSN: | 0014-5793 |
| Popis: | The glucagon-dependent activation of the phosphoenolpyruvate carboxykinase (PCK) gene is modulated by oxygen. It was proposed that heme proteins might function as O2 sensors; their actions are impaired after replacement of the central Fe2+ ion by Co2+ and inhibition of heme synthesis by succinylacetone (SA). Therefore, the effects of CoCl2 and SA, alone and in combination, on the glucagon-dependent induction of PCK activity and PCK mRNA were investigated at different physiological oxygen tensions in primary rat hepatocyte cultures. The cells were exposed to 50 μM CoCl2 and/or 2 mM SA from 4–24 h. After addition of fresh media without CoCl2 or SA, PCK was induced with 1 nM glucagon, PCK activity and PCK mRNA were elevated to 100% at 16% O2 and to about 63% at 8% O2, CoCl2 reduced these increases to about 45% at 16% O2 and to about 35% at 8% O2. SA lowered the inductions to about 50% and 40% each at 16% and 8% O2. CoCl2 plus SA diminished the elevations to about 5% at both oxygen tensions. In the presence of CoCl2 and/or SA, ornithine decarboxylase induction by insulin was not impaired; lactate dehydrogenase did not leak from the cells, which in electron microscopical inspections had normal cell structures. These findings support the hypothesis that a heme protein is involved in the activation of the PCK gene and that it acts as an O2 sensor. |
| Databáze: | OpenAIRE |
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