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 kinase-activated kinases 2 and 3 (MAPKAPK2 and MAPKAPK3) have been implicated in ischemic preconditioning (PC) of the heart to reduce damage following a myocardial infarct. This study examined whether extracellular signal-regulated 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 and 10 min reperfusion increased their activities during global ischemia. Resource Q chromatography resolved two distinct peaks of hsp27 phosphotransferase activities; the first peak (at 0.36 M NaCl) appeared to correspond to the 55-kDa MAPKAPK2. Erk1 activity was elevated in both control and PC hearts after post-ischemic reperfusion, but no change was observed in p70 S6K activity. Infarct size (measured by triphenyltetrazolium staining) in isolated rabbit hearts subjected to 30 min regional ischemia and 2 h reperfusion was 31.0+/-2.6% of the risk zone in controls and was 10.3+/-2.2% in PC hearts (p<0.001). Neither the CK2 inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) nor the Mek1/2 inhibitor PD98059 infused during ischemia blocked protection by PC. The activation of CK2 and Erk1 in ischemic preconditioned hearts appear to be epiphenomena and not required for the reduction of infarction from myocardial ischemia.
Kim
S O
SO
Department of Medicine, University of British Columbia, Vancouver, Canada.
Baines
C P
CP
Critz
S D
SD
Pelech
S L
SL
Katz
S
S
Downey
J M
JM
Cohen
M V
MV
D000818:Animals; D047390:Casein Kinase II; D002852:Chromatography, Ion Exchange; D004789:Enzyme Activation; D005260:Female; D015151:Immunoblotting; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009203:Myocardial Infarction / Q000201:enzymology; D017202:Myocardial Ischemia / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011817:Rabbits; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D000099190:MAP-Kinase-Activated Kinase 2
D047390:Casein Kinase II; D047908:Intracellular Signaling Peptides and Proteins; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D000099190:MAP-Kinase-Activated Kinase 2