Cardioprotective Effect of the Ischemic Preconditioning: Its Relation to Activation of Protein Kinase C.
10.4070/kcj.1999.29.6.602
- Author:
Han Chull KIM
;
Hyun KIM
;
Sung Tak CHUNG
;
Tae Ho KIM
;
Dae Joong KIM
;
Bong Jin RAH
;
Ho Dirk KIM
- Publication Type:Original Article
- Keywords:
Infarct size;
Ischemic preconditioning;
Isolated rabbit heart;
Protein kinase C isozymes
- MeSH:
Antibodies, Monoclonal;
Blotting, Western;
Cytosol;
Heart;
Hemodynamics;
Ischemia;
Ischemic Preconditioning*;
Isoenzymes;
Membranes;
Protein Kinase C*;
Protein Kinases*;
Reperfusion
- From:Korean Circulation Journal
1999;29(6):602-612
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: We tested recent evidences that IP triggers selective activation of protein kinase C (PKC) isozymes using isolated Langendorff-perfused rabbit heart with PKC activator, phorbol ester (PMA, 0.01 nM) or inhibitor (calphostin C, 200 nM). METHODS: After stabilization of baseline hemodynamics, the hearts were subjected to 45 min global ischemia (I) followed by 120 min reperfusion (R) with IP (IP group, n=18) or without IP (ischemic control group, n=16). IP was induced by single episode of 5 min I and 10 min R. In the PMA-treated group (n=19) and calphostin C-treated preconditioned group (n=15), PMA and calphostin C was given for 5 and 15 min before 45 min I, respectively. Myocardial cytosolic and membrane PKC activities were measured by 32P- -ATP incorporation into PKC-specific pepetide: PKC isozymes were analyzed by Western blot with monoclonal antibodies. RESULTS: IP significantly increased the recovery of the LV function including LVDP and coronary flow (p <0.05):however, enhancement of the functional recovery disappeared by calphostin C or PMA treatment. Cytosolic PKC activity decreased to 82-76% in the IP and PMA-treated group (p <0.05): membrane PKC activity increased to 218-272% (p <0.01). However, both fraction of PKC activity was not changed in the calphostin C-treated preconditioned group. In addition, Western blot revealed that PKC- alpha and epsilon, especially epsilon, were selectively translocated during subsequent sustained ischemia after IP or PMA administration. IP and PMA also reduced infarct size (frim 38 to 10-20%, p <0.05). However, calphostin C blocked infarct reduction effect of IP. CONCLUSION: These results indicate that in isolated rabbit heart model, cardioprotective effect of IP may be related, at least in part, to trigger selective translocation of PKC, especially epsilon isotype.
