Ischemia induced activation of heat shock protein 27 kinases and casein kinase 2 in the preconditioned rabbit heart

Protein kinase C (PKC), p38 MAP kinase, and mitogen-activated protein kinas e-activated kinases 2 and 3 (MAPKAPK2 and MAPKAPK3) have been implicated in ischemic preconditioning (PC) of the heart to reduce damage following a my ocardial infarct. This study examined whether extracellular signal-regulate d kinase (Erk) 1, p70 ribosomal S6 kinase (p70 S6K), casein kinase 2 (CK2), and other hsp27 kinases are also activated by PC, and if they are required for protection in rabbit hearts. CK2 and hsp27 kinase activities declined during global ischemia in control hearts, whereas PC with 5 min ischemia an d 10 min reperfusion increased their activities during global ischemia. Res ource Q chromatography resolved two distinct peaks of hsp27 phosphotransfer ase activities; the first peak (at 0.36 M NaCl) appeared to correspond to t he 55-kDa MAPKAPK2. Erk1 activity was elevated in both control and PC heart s after post-ischemic reperfusion, but no change was observed in p70 S6K ac tivity. Infarct size (measured by triphenyltetrazolium staining) in isolate d rabbit hearts subjected to 30 min regional ischemia and 2 h reperfusion w as 31.0 +/- 2.6% of the risk zone in controls and was 10.3 +/- 2.2% in PC h earts (p < 0.001). Neither the CK2 inhibitor 5,6-dichloro-1-beta-D-ribofura nosylbenzimidazole (DRB) nor the Mek1/2 inhibitor PD98059 infused during is chemia blocked protection by PC. The activation of CK2 and Erk1 in ischemic preconditioned hearts appear to be epiphenomena and not required for the r eduction of infarction from myocardial ischemia.