Urocortin protects the heart from reperfusion injury via upregulation of p42/p44 MAPK signaling pathway.

Abstract

Reperfusion of ischemic myocardium is essential for tissue salvage but paradoxically contributes to cell death. We hypothesized that activation of potential survival pathways such as p42/p44 MAPK may prevent lethal reperfusion injury. Urocortin is a peptide factor that affects the p42/p44 MAPK signaling pathway. Both isolated and in vivo rat heart models were used to examine the potential for urocortin to prevent reperfusion injury. Isolated rat hearts underwent 35-min regional ischemia and 2-h reperfusion, with urocortin perfused for 20 min from the onset of reperfusion. In the in vivo study, urocortin was administered as an intravenous bolus 3 min before reperfusion with a protocol of 25-min regional ischemia and 2-h reperfusion. Blockade of the p42/p44 MAPK pathway with the inhibitor PD-98059 was used in both models. Urocortin attenuated lethal reperfusion-induced injury both in vitro and in vivo via a p42/p44 MAPK-dependent mechanism. Furthermore, Western blot analysis demonstrated the ability of urocortin to directly upregulate this signaling pathway. In conclusion, we believe that the p42/p44 MAPK-dependent signaling pathway represents an important survival mechanism against reperfusion injury.

• Authors: Daniel Schulman, David S Latchman, Derek M Yellon
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 283 Issue 4 Pg. H1481-8 (Oct 2002) ISSN: 0363-6135 [Print] United States
• PMID: 12234800 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Flavonoids
• Neuroprotective Agents
• Urocortins
• Corticotropin-Releasing Hormone
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Animals
• Blood Gas Analysis
• Blood Pressure (drug effects)
• Corticotropin-Releasing Hormone (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Flavonoids (pharmacology)
• Heart Rate (drug effects)
• Hypotension (chemically induced, pathology)
• In Vitro Techniques
• MAP Kinase Signaling System (drug effects)
• Male
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases (metabolism)
• Myocardial Infarction (drug therapy, metabolism, pathology)
• Myocardial Reperfusion Injury (drug therapy, metabolism, pathology)
• Neuroprotective Agents (pharmacology)
• Phosphorylation (drug effects)
• Rats
• Rats, Sprague-Dawley
• Up-Regulation (drug effects)
• Urocortins