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.
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.
Marterre
W F
WF
Department of Surgery, University of Kentucky College of Medicine, Lexington.
Kindy
M S
MS
Carney
J M
JM
Landrum
R W
RW
Strodel
W E
WE
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D003600:Cytosol / Q000378:metabolism; D005609:Free Radicals; D005786:Gene Expression Regulation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007511:Ischemia / Q000378:metabolism; D008099:Liver / Q000098:blood supply*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009589:Nitrogen Oxides / Q000494:pharmacology*; D011519:Proto-Oncogenes / Q000502:physiology*; D012313:RNA / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000378:metabolism*; D013997:Time Factors
D005609:Free Radicals; D009589:Nitrogen Oxides; C015388:nitrones; D012313:RNA; D000255:Adenosine Triphosphate