Rapid activation of NF-κB and AP-1 and target gene expression in postischemic rat intestine

Background & Aims: The molecular mechanisms underlying intestinal mucosal damage-repair processes induced by: ischemia-reperfusion (IR) remain unknown, We determined nuclear factor-kappa B (NF-kappa B) and activator protein 1 (AP-1) activities and the expression of potential target genes relevant to damage-repair events. Methods: Rat jejunal segment was subjected to ischemia for 30 minutes followed by reperfusion for defined times. NF-kappa B and AP-1 activities; mucosal p105, p50, and inhibitor kappa B-alpha (I kappa B-alpha) levels; and c-fos, neurotensin, and ferritin H expression were determined by electrophoretic mobility shift assay and Western and Northern analyses, respectively, Results: NF-kappa B and AP-1 activities were significantly elevated from 1 to 12 hours after reperfusion, The activated NF-kappa B in the nuclear extract consisted of solely p50 homodimers, Activation of p50 was associated with a decrease of p105, generation of p50, and increased phosphorylation and degradation of I kappa B-alpha, The activated AP-1 contained c-fos but not c-jun, fosB, and Fra-1. Reperfusion induced a transient elevation of c-fos, prolonged increase of neurotensin, and early reduction followed by recovery of ferritin H messenger RNA, Conclusions: The intestine shows organ-specific responses to IR, characterized by prolonged NF-kappa B and AP-1 activation involving NF-kappa B p50 dimers and excluding AP-1 c-jun protein. Degradation of the I kappa B-gamma component of p105 and partial reduction I kappa B-alpha selectively activate p50/p50 dimers, Temporal patterns of target gene expression reflect functional relevance to mucosal damage-repair processes after IR.