Activation Time Course of Activator Protein-1 and Effect of Proline Dithiocarbamate During Ischemia-Reperfusion in Rat Skeletal Muscle

Abstract

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.

NF‐κB plays a major role during the systemic and local acute inflammatory response following intestinal reperfusion injury

“…The contribution of these transcription factors to the inflammatory response has been demonstrated in several models of acute severe inflammation. A few studies have evaluated the potential contribution of AP‐1 and NF‐ κ B to ischaemia and reperfusion (I/R) injury using genetic (Chen et al ., 2003; Fan et al ., 2004) and pharmacological strategies (Lefler et al ., 2002; Pye et al ., 2003; Zingarelli et al ., 2003; Zou et al ., 2003). However, most studies have used nonspecific inhibitors of transcription factor translocation and few have attempted to compare the relative contribution of AP‐1 and NF‐ κ B to I/R injury.…”

Training‐induced mitochondrial adaptation: role of peroxisome proliferator‐activated receptor γ coactivator‐1α, nuclear factor‐κB and β‐blockade

“…Furthermore, p38 MAPK was proposed to play a major role in PGC‐1α downregulation in cardiac cells (Palomer et al 2009). In contrast, inhibition of NFκB by pyrolidine dithiocarbamate (PDTC) treatment has been shown to ameliorate skeletal muscle dysfunction caused by muscular dystrophy (Carlson et al 2005), ischaemia–reperfusion (Lefler et al 2002) and overexpression of inducible nitric oxide synthase (Adams et al 2002). Given that NFκB can be activated by muscular contraction, due to increased ROS production, and is implicated in the upregulation of a wide range of redox‐sensitive genes (Ji et al 2004; Ji, 2008), the interaction of NFκB and PDTC on overall muscle adaptation to exercise, especially with regard to PGC‐1α‐induced mitochondrial biogenesis, would be of great importance in understanding the mechanisms underlining these changes.…”