Increased expression and altered subcellular distribution of PKC-delta in chronically hypoxic rat myocardium: involvement in cardioprotection
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
15576445
DOI
10.1152/ajpheart.00586.2004
PII: 00586.2004
Knihovny.cz E-resources
- MeSH
- Chronic Disease MeSH
- Hematocrit MeSH
- Hypoxia metabolism MeSH
- Myocardial Infarction metabolism MeSH
- Enzyme Inhibitors pharmacology MeSH
- Blood Pressure MeSH
- Rats MeSH
- Myocardium enzymology MeSH
- Rats, Wistar MeSH
- Protein Kinase C-delta MeSH
- Protein Kinase C-epsilon MeSH
- Protein Kinase C antagonists & inhibitors metabolism MeSH
- Myocardial Reperfusion Injury metabolism MeSH
- Heart Rate MeSH
- Heart Ventricles enzymology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Enzyme Inhibitors MeSH
- Prkcd protein, rat MeSH Browser
- Prkce protein, rat MeSH Browser
- Protein Kinase C-delta MeSH
- Protein Kinase C-epsilon MeSH
- Protein Kinase C MeSH
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 7,000 m for 8 h/day, 5 days/wk; the total number of exposures was 24-32. A control group was kept under normoxic conditions. 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. The PKC inhibitors chelerythrine (1 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 nuclear-cytoskeletal, mitochondrial, and microsomal fractions of chronically hypoxic myocardium by 100%, 212%, 237%, and 146%, respectively, compared with 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 the 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 hypoxia-induced cardioprotection in rats is partially mediated by PKC-delta; the contribution of other isoforms remains to be determined.
References provided by Crossref.org
Sixty Years of Heart Research in the Institute of Physiology of the Czech Academy of Sciences
The involvement of protein kinases in the cardioprotective effect of chronic hypoxia
Up-regulation and redistribution of protein kinase C-δ in chronically hypoxic heart
