Inactivation of the MEK/ERK pathway in the myocardium during cardiopulmonary bypass

Citation
Eg. Araujo et al., Inactivation of the MEK/ERK pathway in the myocardium during cardiopulmonary bypass, J THOR SURG, 121(4), 2001, pp. 773-781
Citations number
36
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
ISSN journal
00225223 → ACNP
Volume
121
Issue
4
Year of publication
2001
Pages
773 - 781
Database
ISI
SICI code
0022-5223(200104)121:4<773:IOTMPI>2.0.ZU;2-F
Abstract
Objectives: A general pro-inflammatory response after cardiopulmonary bypas s (CPB) may involve changes in signal transduction and in part be responsib le for arrhythmias and myocardial dysfunction after cardiac surgery. The ME K/ERK (mitogen-activated protein kinase kinase/extracellular regulated kina se) pathway is common to many stimuli and may play a pivotal role in morbid ity 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 minu tes of normothermic CPB and after 90 minutes of post-CPB perfusion. The act ivities and protein levels of kinases MEK1/2, ERK1/2, a cellular tyrosine k inase (c-Src), protein kinase B (Akt), and the protein levels of mitogen-ac tivated protein kinase phosphatase (MKP-1) were studied by immunoblotting v entricular and atrial myocardium lysates and labeling sections with antibod ies 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 vent ricular and atrial myocardium with an increase in MKP-1, a negative regulat or of ERK 1/2. 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 cont rols. The decrease of ERK1/2 and MEK1/2 phosphorylation 90 minutes after te rmination 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 m echanisms in the MEK/ERK signal transduction machinery in myocardium subjec ted to CPB.