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Am J Physiol Heart Circ Physiol (December 2, 2004). doi:10.1152/ajpheart.00586.2004
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Submitted on June 14, 2004
Accepted on November 24, 2004

Increased expression and altered subcellular distribution of PKC isoform {delta} in chronically hypoxic rat myocardium: involvement in cardioprotection

Jan Neckar1, Irena Markova2, Frantisek Novak2, Olga Novakova2, Ondrej Szarszoi1, Bohuslav Ostadal1, and Frantisek Kolar1*

1 Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
2 Centre for Experimental Cardiovascular Research, Prague, Czech Republic

* To whom correspondence should be addressed. E-mail: kolar{at}biomed.cas.cz.

We examined the role of protein kinase C (PKC) in the cardioprotective mechanism induced by long-term adaptation to chronic intermittent hypoxia. Adult male Wistar rats were exposed to hypobaric hypoxia of 7000 m for 8 h/day, 5 days/week; the total number of exposures was 24-32. A control group was kept under normoxic conditions. The Western blot analysis of PKC isoforms {delta} and {epsilon} was performed in the cytosol and three particulate fractions of left ventricular myocardium. Infarct size was determined in open-chest animals subjected to 20-min coronary artery occlusion and 3-h reperfusion. PKC inhibitors chelerythrine (1 mg/kg or 5 mg/kg) or rottlerin (selective for PKC{delta} isoform; 0.3 mg/kg) were administered intravenously as a single bolus 15 min before ischemia. Chronic hypoxia had no effect on the expression and distribution of PKC{epsilon}. The relative amount of PKC{delta} increased in the cytosol and nuclearcytoskeletal, mitochondrial and microsomal fractions of chronically hypoxic myocardium by 100%, 212%, 237%, and 146%, respectively, compared to corresponding normoxic values. Chronic hypoxia decreased the size of myocardial infarction (normalized to the area at risk) by about one-third on the average (P<0.05). Both doses of chelerythrine tended to reduce infarction in controls and only its high dose completely abolished the improvement of ischemic tolerance in hypoxic hearts (P<0.05). Rottlerin attenuated the infarct size-limiting effect of chronic hypoxia (P<0.05) and it had no effect in controls. These results suggest that chronic intermittent hypoxiainduced cardioprotection in rats is partially mediated by PKC{delta}; the contribution of other isoforms remains to be determined.




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