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

FEBS Letters

Kietzmann, Thomas¹  Jungermann, Kurt¹  Schmidt, Helga¹  Probst, Irmelin¹ 

[1] Institut für Biochemie und Molekulare Zellbiologie, Humboldtallee 23, D-3400 Göttingen, Germany

关键词: Metabolic zonation;    Phosphoenolpyruvate carboxykinase gene;    Heme protein;    Hepatic oxygen sensing;    Glucagon;   

DOI  :  10.1016/0014-5793(92)81113-Z

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown