Induction of the protooncogene c-fos and recovery of cytosolic adenosine triphosphate in reperfused liver after transient warm ischemia: effect of nitrone free-radical spin-trap agents.

Abstract

Ischemia and reperfusion stimulate several adenosine triphosphate (ATP)-dependent processes involving release of substances including free radicals. This cellular response is mediated through receptors responsive to transcriptional products of gene expression; c-fos acts as a transcriptional factor involved in the regulation of genes associated with cellular proliferation and differentiation. We hypothesized that nitrone free-radical spin traps promote restoration of cytosolic ATP during reperfusion and prevent c-fos induction. Four control rats had no ischemia. Global hepatic ischemia was induced in 19 rats in four groups: saline solution, phenyl-N-tert-butyl nitrone (PBN), alpha 1-pyridyl-N-oxide N-tert-butyl nitrone (POBN), and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). ATP and intracellular pH were measured at intervals before, during, and after ischemia. At 90 minutes of reperfusion, liver c-fos mRNA was measured. A fourfold elevation of c-fos occurred in the saline-treated group (p less than 0.001). PBN and POBN groups did not differ from the saline group. DMPO resulted in significantly less induction of c-fos than did NS. ATP depletion and recovery in all treatment groups was similar to that of the saline group. We conclude that (1) nitrone spin traps do not prevent c-fos induction or alter the pattern of ATP recovery after hepatic ischemia and reperfusion and (2) c-fos induction is not necessary for restoration of ATP, but the rate of ATP restoration is inversely related to c-fos induction.

• Authors: W F Marterre Jr, M S Kindy, J M Carney, R W Landrum, W E Strodel
• Journal: Surgery (Surgery) Vol. 110 Issue 2 Pg. 184-91 (Aug 1991) ISSN: 0039-6060 [Print] United States
• PMID: 1713356 (Publication Type: Journal Article)

Chemical References

• Free Radicals
• Nitrogen Oxides
• nitrones
• RNA
• Adenosine Triphosphate

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Blotting, Northern
• Cytosol (metabolism)
• Free Radicals
• Gene Expression Regulation (drug effects)
• Hydrogen-Ion Concentration
• Ischemia (metabolism)
• Liver (blood supply)
• Magnetic Resonance Spectroscopy
• Male
• Nitrogen Oxides (pharmacology)
• Proto-Oncogenes (physiology)
• RNA (isolation & purification)
• Rats
• Rats, Inbred Strains
• Reperfusion Injury (metabolism)
• Time Factors