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Updated: Jul 11, 2026
Acute Myocardial Infarction in Rats
Published on: February 16, 2011
Rapid activation of NF-kappaB and AP-1 and target gene expression in postischemic rat intestine
1Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Background & Aims:
The molecular mechanisms underlying intestinal mucosal damage-repair processes induced by ischemia-reperfusion (IR) remain unknown. We determined nuclear factor-kappaB (NF-kappaB) 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-kappaB and AP-1 activities; mucosal p105, p50, and inhibitor kappaB-alpha (IkappaB-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-kappaB and AP-1 activities were significantly elevated from 1 to 12 hours after reperfusion. The activated NF-kappaB 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 IkappaB-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-kappaB and AP-1 activation involving NF-kappaB p50 dimers and excluding AP-1 c-jun protein. Degradation of the IkappaB-gamma component of p105 and partial reduction IkappaB-alpha selectively activate p50/p50 dimers. Temporal patterns of target gene expression reflect functional relevance to mucosal damage-repair processes after IR.
Insights
Investigating intestinal ischemia-reperfusion (IR) injury, this study reveals prolonged activation of nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) pathways. These molecular events are crucial for understanding intestinal damage-repair mechanisms following IR.
Area of Science:
- Gastroenterology
- Molecular Biology
- Cellular Biology
Background:
- Intestinal mucosal damage-repair processes following ischemia-reperfusion (IR) are not fully understood.
- Key molecular signaling pathways involved in these processes require elucidation.
Purpose of the Study:
- To investigate the roles of nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) in intestinal mucosal damage-repair after IR.
- To determine the expression patterns of genes associated with damage-repair events.
Main Methods:
- Rat jejunal segments underwent 30 minutes of ischemia followed by reperfusion.
- NF-kappaB and AP-1 activities were measured using electrophoretic mobility shift assays.
- Protein and mRNA levels of specific target genes (p105, p50, IkappaB-alpha, c-fos, neurotensin, ferritin H) were analyzed via Western and Northern blotting.
Main Results:
- NF-kappaB and AP-1 activities significantly increased from 1 to 12 hours post-reperfusion.
- Activated NF-kappaB comprised solely p50 homodimers, linked to IkappaB-alpha degradation.
- Activated AP-1 included c-fos but not c-jun; neurotensin and c-fos expression were altered, while ferritin H mRNA showed dynamic changes.
Conclusions:
- Intestinal IR elicits organ-specific responses characterized by sustained NF-kappaB and AP-1 activation.
- Specific molecular mechanisms involving p50 homodimers and exclusion of c-jun protein define AP-1 activity.
- The temporal expression of target genes correlates with intestinal mucosal damage-repair processes post-IR.
