Effect of the Rho kinase inhibitor Y-27632 on the proteome of hearts with ischemia-reperfusion injury.

Abstract

Growing attention has been given to the role of the Rho kinase pathway in the development of heart disease and ischemia/reperfusion (I/R) injury. Y-27632 is a Rho kinase inhibitor demonstrated to protect against I/R injury, but the exact mechanism by which it does so remains to be elucidated. The goal of this project was to determine new targets by which Y-27632 can protect the heart against I/R injury. Isolated rat hearts were perfused under aerobic conditions or subjected to I/R in the presence or absence of Y-27632. Administration of Y-27632 (1 μM) before ischemia and during the first 10 min of reperfusion resulted in complete recovery of cardiac function. 2-D electrophoresis followed by MS identified four proteins whose levels were affected by Y-27632 treatment. Lactate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase were significantly increased in the Y-27632 treated group, while creatine kinase was normalized to control levels. In addition, we found increased level of two different molecular fragments of ATP synthase, which were normalized by Y-27632. This increase suggests that during ischemia ATP synthase is subjected to degradation. The changes in metabolic enzymes' levels and their regulation by Y-27632 suggest that the cardioprotective effect of Y-27632 involves increased energy production.

• Authors: Virgilio J J Cadete, Jolanta Sawicka, Dorota Polewicz, Adrian Doroszko, Mieczyslaw Wozniak, Grzegorz Sawicki
• Journal: Proteomics (Proteomics) Vol. 10 Issue 24 Pg. 4377-85 (Dec 2010) ISSN: 1615-9861 [Electronic] Germany
• PMID: 21136592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Amides
• Protein Kinase Inhibitors
• Protein Subunits
• Proteome
• Pyridines
• Y 27632
• rho-Associated Kinases
• Mitochondrial Proton-Translocating ATPases

Topics

• Amides (pharmacology)
• Amino Acid Sequence
• Animals
• Male
• Mitochondrial Proton-Translocating ATPases (metabolism)
• Molecular Sequence Data
• Myocardial Contraction (drug effects)
• Myocardial Reperfusion Injury (metabolism, physiopathology)
• Myocardium (metabolism)
• Protein Kinase Inhibitors
• Protein Subunits (metabolism)
• Proteome (metabolism)
• Pyridines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• rho-Associated Kinases (antagonists & inhibitors)