Activation time course of activator protein-1 and effect of proline dithiocarbamate during ischemia-reperfusion in rat skeletal muscle.
Activator protein 1 (AP-1) is thought to play an important role in the expression of genes expressed in response to ischemia-reperfusion injury. In this report, the activation of AP-1 in rat skeletal muscle during reperfusion after a 4-hour ischemic period was studied. AP-1 activation displayed a biphasic pattern, showing peak activities at 1 hour after perfusion and from 4 hours to 12 hours after perfusion. Inhibition of AP-1 activation was investigated using a potent nuclear factor kappa B inhibitor, proline dithiocarbamate (Pro-DTC). AP-1 binding activity at 1 hour of reperfusion was significantly reduced (29.0 +/- 10.1% SEM; p < 0.05) after intravenous administration of Pro-DTC (n = 7 animals in each group). Further elucidation of the role of AP-1 is warranted in hopes of developing strategies to reduce the deleterious effects of ischemia-reperfusion injury.
Lefler
Scott R
SR
Mayo Clinic Scottsdale, Scottsdale, Arizona, USA.
Lille
Sean T
ST
Huemer
Georg M
GM
Tucker
Ross
R
Murray
Terri
T
Schoeller
Thomas
T
Mulligan
David C
DC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D013859:Thiocarbamates / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D000975:Antioxidants; D013859:Thiocarbamates; D018808:Transcription Factor AP-1; C066229:prolinedithiocarbamate; D011392:Proline