Role of microtubules in ischemic preconditioning against myocardial infarction.
OBJECTIVE
The role of microtubules in ischemic preconditioning (PC) was investigated in isolated perfused rabbit hearts.


METHODS
Myocardial infarction was induced by 30-min global ischemia and 2-h reperfusion, and infarct size was expressed as a percentage of the left ventricle (%IS/LV). Using separate groups of rabbits, ventricular biopsies were taken before and after PC for determination of protein kinase C (PKC) translocation and p38-mitogen-activated protein kinase (p38MAP kinase) activation. To depolymerize microtubules, we used two structurally different agents, colchicine (50 microM) and nocodazole (1 microM).


RESULTS
PC with two cycles of 5-min ischemia/5-min reperfusion significantly reduced infarct size from 60.1+/-5.0% to 20.0+/-5.0%. Although neither colchicine nor nocodazole modified infarct size in nonpreconditioned hearts, these agents abolished the infarct size-limiting effects of PC (%IS/LV=56.1+/-6.0% and 53.5+/-2.5%, respectively). Colchicine prevented translocation of PKC-epsilon and p38MAP kinase activation by PC. PKC translocation by infusion of 1-oleyl-2-acetyl-sn-glycerol in nonischemic hearts was also prevented by colchicine.


CONCLUSIONS
Microtubules play a crucial role in the development of anti-infarct tolerance by PC as a mechanism supporting translocation of activated PKC.
Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, South-1 West-16, Chuo-ku, Sapporo 060-8543, Japan.
Yuichi
Y
Nakamura
Tetsuji
T
Miura
Atsushi
A
Nakano
Yoshihiko
Y
Ichikawa
Toshiyuki
T
Yano
Hironori
H
Kobayashi
Yoshihiro
Y
Ikeda
Takayuki
T
Miki
Kazuaki
K
Shimamoto
D000818:Animals; D001692:Biological Transport; D003078:Colchicine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008870:Microtubules / Q000502:physiology* / Q000648:ultrastructure; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D015739:Nocodazole / Q000494:pharmacology; D010477:Perfusion; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis
D004791:Enzyme Inhibitors; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D015739:Nocodazole; D003078:Colchicine