Remote vs. ischaemic preconditioning: the differential role of mitogen-activated protein kinase pathways.
OBJECTIVE
Since mitogen-activated protein kinases (MAPKs) were found to be implicated in the signalling of ischaemic preconditioning (IPC), we tested the hypothesis of a contribution of these protein kinases to remote preconditioning (RPC).


RESULTS
To determine the role of p38, ERK1/2, and JNK1/2 MAPKs in mediating cardiac protection, an in vivo model of myocardial infarction was applied in male Wistar rats. RPC or IPC was induced by occlusion of the superior mesenteric artery or the left coronary artery, respectively. Infarct size (IS) was determined based on 2,3,5-triphenyltetrazolium chloride staining. Phosphorylation of the various MAPKs was analysed by immunoblotting in samples of the small intestine and myocardium obtained after IPC or RPC procedures. The MAPK inhibitors SB203580 (p38), PD98059 (ERK1/2), and SP600125 (JNK1/2) were administered to assess the potential significance of MAPK signalling in RPC. Both preconditioning stimuli decreased myocardial IS significantly after a lethal period of ischaemia. Each of the applied MAPK inhibitors was capable of abrogating the RPC-induced cardioprotection. Western blot analysis of myocardial samples revealed an increase in phosphorylated amounts of ERK1/2 and JNK1 after IPC, whereas phosphorylation of p38 protein was decreased significantly. Likewise, RPC resulted in a considerable increase in phosphorylation of ERK1/2 and JNK1/2 proteins in the small intestine, whereas it did not alter the MAPK phosphorylation state in the myocardium.


CONCLUSIONS
All investigated MAPK pathways appear to be involved in RPC-induced cardioprotection; however, they do not contribute to the alterations that define the preconditioned state of the myocardium prior to the infarction.
Heidbreder
Marc
M
Institute of Experimental and Clinical Pharmacology and Toxicology, University Hospital Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany. heidbred@medinf.mu-luebeck.de
Naumann
Annegret
A
Tempel
Klaus
K
Dominiak
Peter
P
Dendorfer
Andreas
A
D000818:Animals; D015153:Blotting, Western; D006439:Hemodynamics; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D047428:Protein Kinase Inhibitors; D048056:Mitogen-Activated Protein Kinase 9; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases