The stress-responsive MAP kinase p38 is activated by low-flow ischemia in the in situ porcine heart.
Stress-responsive p38 MAP kinase is activated by phosphorylation during global and severe regional myocardial ischemia. However, it is unknown whether or not moderate, low-flow ischemia also activates p38 MAP kinase. Therefore, we investigated p38 MAP kinase activation in an established model of short-term hibernation and stunning. In anesthetized swine, coronary blood flow into the left anterior descending coronary artery was decreased in order to reduce regional contractile function by identical with 50%. Transmural myocardial biopsies were taken before (controls) and during ischemia as well as after reperfusion. Creatine phosphate content, after an early ischemic reduction, recovered to control values at 90 min ischemia. The expression of phospholamban, SERCA2a, calsequestrin, and troponin inhibitor was unchanged under these conditions (Northern and Western blotting). At 8 min of ischemia, however, p38 MAP kinase was activated to 221% of the pre-ischemic value as judged by its elevated phosphorylation state. Then, it returned to control values by 85 min ischemia. We conclude that low-flow ischemia transiently activates the stress-responsive p38 MAP kinase which might act to trigger cardioprotective events.
Lüss
H
H
Institut für Pharmakologie und Toxikologie, Westfälische Wilhelms-Universität Münster, Münster, D-48129, Germany. luss@uni-muenster.de
Neumann
J
J
Schmitz
W
W
Schulz
R
R
Heusch
G
G
D000818:Animals; D001706:Biopsy; D015152:Blotting, Northern; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis; D002155:Calsequestrin / Q000096:biosynthesis; D002339:Carotid Arteries / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism; D004789:Enzyme Activation; D006321:Heart / Q000502:physiology; D007601:Jugular Veins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017202:Myocardial Ischemia; D009206:Myocardium / Q000201:enzymology*; D010766:Phosphorylation; D015427:Reperfusion Injury; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013552:Swine; D013997:Time Factors; D014336:Troponin / Q000037:antagonists & inhibitors; D048051:p38 Mitogen-Activated Protein Kinases; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D002155:Calsequestrin; D020928:Mitogen-Activated Protein Kinases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D014336:Troponin; D048051:p38 Mitogen-Activated Protein Kinases; D000099211:Phospholamban