Inactivation of the MEK/ERK pathway in the myocardium during cardiopulmonary bypass
| Autor: | X.Alec Li, Eugenio G. Araujo, Frank W. Sellke, Kaori Sato, Renato Faro, Cesario Bianchi |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
MAPK/ERK pathway Pulmonary and Respiratory Medicine medicine.medical_specialty Swine Heart Ventricles Immunoblotting Protein Serine-Threonine Kinases CSK Tyrosine-Protein Kinase src Homology Domains Internal medicine Animals Medicine Heart Atria Phosphorylation Protein kinase A Protein kinase B Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase Kinases Cardiopulmonary Bypass Microscopy Confocal biology business.industry Kinase Myocardium Protein-Tyrosine Kinases src-Family Kinases surgical procedures operative Endocrinology Mitogen-activated protein kinase biology.protein Female Surgery Signal transduction business Cardiology and Cardiovascular Medicine Tyrosine kinase Biomarkers Signal Transduction |
| Zdroj: | The Journal of Thoracic and Cardiovascular Surgery. 121(4):773-781 |
| ISSN: | 0022-5223 |
| DOI: | 10.1067/mtc.2001.112933 |
| Popis: | Objectives: A general pro-inflammatory response after cardiopulmonary bypass (CPB) may involve changes in signal transduction and in part be responsible for arrhythmias and myocardial dysfunction after cardiac surgery. The MEK/ERK (mitogen-activated protein kinase kinase/extracellular regulated kinase) pathway is common to many stimuli and may play a pivotal role in morbidity associated with CPB. We investigated the changes in MEK/ERK pathway and related enzymes after CPB in pigs. Methods: We examined ventricular and atrial tissue from pigs before 90 minutes of normothermic CPB and after 90 minutes of post-CPB perfusion. The activities and protein levels of kinases MEK1/2, ERK1/2, a cellular tyrosine kinase (c-Src), protein kinase B (Akt), and the protein levels of mitogen-activated protein kinase phosphatase (MKP-1) were studied by immunoblotting ventricular and atrial myocardium lysates and labeling sections with antibodies that recognize the activated forms of the kinases and the phosphatase. Control pigs were subjected to sternotomy and heparinization but not CPB. Results: We found a consistent inactivation of MEK/ERK pathway in both ventricular and atrial myocardium with an increase in MKP-1, a negative regulator of ERK1/2. The activities and protein levels of c-Src and Akt were not significantly modified before or after CPB, suggesting a certain degree of specificity for the MEK/ERK pathway. Such changes were not observed in controls. The decrease of ERK1/2 and MEK1/2 phosphorylation 90 minutes after termination of CPB (as well as the increase of nuclear MKP-1 protein levels) was also apparent by confocal microscopy. Conclusions: These results collectively reveal a prevalence of inhibitory mechanisms in the MEK/ERK signal transduction machinery in myocardium subjected to CPB. (J Thorac Cardiovasc Surg 2001;121:773-81) |
| Databáze: | OpenAIRE |
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