Xenon preconditioning differently regulates p44/42 MAPK (ERK 1/2) and p46/54 MAPK (JNK 1/2 and 3) in vivo.
BACKGROUND
Xenon (Xe) induces preconditioning (PC) of the rat heart in vivo via activation of p38 mitogen-activated protein kinase (MAPK). The role of ERK 1/2 and JNK 1/2 and 3 in Xe-PC has yet not been determined.


METHODS
For infarct size measurements, anaesthetized rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Animals received Xe 70% during three 5 min periods with and without the ERK inhibitor PD 98059 (1 mg kg(-1), PD) or the JNK inhibitor SP 600125 (6 mg kg(-1), SP) (n=10 per group). Additional hearts were excised for western blot and kinase activity assay: without further treatment, after the first, the second and the third period of Xe-PC or at the end of the last washout phase (n=4 each).


RESULTS
Infarct size (% of area at risk) was reduced from 46.2 (8.1)% to 28.4 (11.3)% after Xe-PC (P<0.01). PD completely abolished this effect [49.7 (11.4)%, P<0.01 vs Xe-PC]. The ratio of particulate/cytosolic phospho ERK 1/2 was time dependently increased during the PC protocol [ERK 1: 15 min: 2.4 (1.2), 25 min: 1.5 (0.3), 35 min: 1.6 (0.7), 45 min: 1.5 (0.5) vs Con 1.0 (0.5) and ERK 2: 15 min: 3.3 (1.8), 25 min: 2.0 (1.5), 35 min: 1.8 (1.7), 45 min: 0.9 (0.6) vs Con 0.8 (0.4)]. This finding was confirmed by a non-radioactive MAPK activity assay. In contrast SP had no effect on Xe-PC and the phosphorylation state of JNK was not influenced by Xe-PC.


CONCLUSIONS
Besides the p38 MAPK, ERK 1/2 also is a mediator of Xe-PC. However, JNK is not involved, demonstrating a highly specific regulation of different kinases during Xe-PC.
Weber
N C
NC
Department of Anaesthesiology, University Hospital of Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany. N.C.Weber@amc.uva.nl
Stursberg
J
J
Wirthle
N M
NM
Toma
O
O
Schlack
W
W
Preckel
B
B
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014978:Xenon / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D014978:Xenon; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1