Activation of signaling pathways and regulatory mechanisms of mRNA translation following myocardial ischemia-reperfusion.

Abstract

Protein expression in the heart is altered following periods of myocardial ischemia. The changes in protein expression are associated with increased cell size that can be maladaptive. There is little information regarding the regulation of protein expression through the process of mRNA translation during ischemia and reperfusion in the heart. Therefore, the purpose of this study was to identify changes in signaling pathways and downstream regulatory mechanisms of mRNA translation in an in vivo model of myocardial ischemia and reperfusion. Hearts were collected from rats whose left main coronary arteries had either been occluded for 25 min or reversibly occluded for 25 min and subsequently reperfused for 15 min. Following reperfusion, both the phosphoinositide 3-kinase and mitogen-activated protein kinase pathways were activated, as evidenced by increased phosphorylation of Akt (PKB), extracellular signal-regulated kinase 1/2, and p38 mitogen-activated protein kinase. Activation of Akt stimulated signaling through the protein kinase mammalian target of rapamycin, as evidenced by increased phosphorylation of two of its effectors, the ribosomal protein S6 kinase and the eukaryotic initiation factor eIF4E binding protein 1. Ischemia and reperfusion also resulted in increased phosphorylation of eIF2 and eIF2B. These changes in protein phosphorylation suggest that control of mRNA translation following ischemia and reperfusion is modulated through a number of signaling pathways and regulatory mechanisms.

• Authors: Stephen J Crozier, Xueqian Zhang, Jufang Wang, Joseph Cheung, Scot R Kimball, Leonard S Jefferson
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 101 Issue 2 Pg. 576-82 (Aug 2006) ISSN: 8750-7587 [Print] United States
• PMID: 16690784 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Eukaryotic Initiation Factor-2
• Eukaryotic Initiation Factor-2B
• Eukaryotic Initiation Factor-4E
• Protein Kinases
• Ribosomal Protein S6 Kinases
• TOR Serine-Threonine Kinases
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Eukaryotic Initiation Factor-2 (metabolism)
• Eukaryotic Initiation Factor-2B (metabolism)
• Eukaryotic Initiation Factor-4E (metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Heart (physiopathology)
• Hypoxia (physiopathology)
• Male
• Myocardial Reperfusion Injury (physiopathology)
• Protein Biosynthesis (physiology)
• Protein Kinases (metabolism)
• Rats
• Rats, Sprague-Dawley
• Ribosomal Protein S6 Kinases (metabolism)
• Signal Transduction (physiology)
• TOR Serine-Threonine Kinases