Ischemic preconditioning phosphorylates mitogen-activated kinases and heat shock protein 27 in the diabetic rat heart.
Diabetes mellitus blocks protection by ischemic preconditioning (IPC), but the mechanism is not known. We investigated the effect of ischemic preconditioning on mitogen-activated protein kinases (extracellular signal-regulated kinases 1 and 2, c-Jun N-terminal kinases, p38 mitogen-activated kinase) and heat shock protein 27 phosphorylation in diabetic and nondiabetic rat hearts in vivo. Two groups of anaesthetized nondiabetic and diabetic rats underwent a preconditioning protocol (3 cycles of 3 min coronary artery occlusion and 5 min of reperfusion). Two further groups served as untreated controls. Hearts were excised for protein measurements by Western blot. Four additional groups underwent 25 min of coronary occlusion followed by 2 h of reperfusion to induce myocardial infarction. In these animals, infarct size was measured. IPC reduced infarct size in the nondiabetic rats but not in the diabetic animals. In diabetic rats, IPC induced phosphorylation of the mitogen-activated protein kinases and of heat shock protein 27. We conclude that protection by IPC is blocked by diabetes mellitus in the rat heart in vivo without affecting phosphorylation of mitogen-activated protein kinases or heat shock protein 27. Therefore, the blockade mechanism of diabetes mellitus is downstream of mitogen-activated kinases and heat shock protein 27.
Ebel
D
D
Klinik für Anästhesiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany. D.Ebel@ic.umcn.nl
Toma
O
O
Appler
S
S
Baumann
K
K
Frässdorf
J
J
Preckel
B
B
Rösen
P
P
Schlack
W
W
Weber
N C
NC
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial / Q000662:veterinary; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
D055551:HSP27 Heat-Shock Proteins; D013311:Streptozocin; D048049:Extracellular Signal-Regulated MAP Kinases