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 ratheart in vivo via activation of p38 mitogen-activated proteinkinase (MAPK). The role of ERK 1/2 and JNK 1/2 and 3 in Xe-PChas yet not been determined. Methods. For infarct size measurements, anaesthetized rats weresubjected to 25 min of coronary artery occlusion followed by120 min of reperfusion. Animals received Xe 70% during three5 min periods with and without the ERK inhibitor PD 98059 (1mg kg^–1, PD) or the JNK inhibitor SP 600125 (6 mg kg^–1,SP) (n=10 per group). Additional hearts were excised for westernblot and kinase activity assay: without further treatment, afterthe first, the second and the third period of Xe-PC or at theend 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 completelyabolished this effect [49.7 (11.4)%, P<0.01 vs Xe-PC]. Theratio of particulate/cytosolic phospho ERK 1/2 was time dependentlyincreased 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 Con1.0 (0.5) and ERK 2: 15 min: 3.3 (1.8), 25 min: 2.0 (1.5), 35min: 1.8 (1.7), 45 min: 0.9 (0.6) vs Con 0.8 (0.4)]. This findingwas confirmed by a non-radioactive MAPK activity assay. In contrastSP had no effect on Xe-PC and the phosphorylation state of JNKwas not influenced by Xe-PC. Conclusion. Besides the p38 MAPK, ERK 1/2 also is a mediatorof Xe-PC. However, JNK is not involved, demonstrating a highlyspecific regulation of different kinases during Xe-PC.