Increased expression and altered subcellular distribution of PKC-delta in chronically hypoxic rat myocardium: involvement in cardioprotection
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
15576445
DOI
10.1152/ajpheart.00586.2004
PII: 00586.2004
Knihovny.cz E-zdroje
- MeSH
- chronická nemoc MeSH
- hematokrit MeSH
- hypoxie metabolismus MeSH
- infarkt myokardu metabolismus MeSH
- inhibitory enzymů farmakologie MeSH
- krevní tlak MeSH
- krysa rodu Rattus MeSH
- myokard enzymologie MeSH
- potkani Wistar MeSH
- proteinkinasa C-delta MeSH
- proteinkinasa C-epsilon MeSH
- proteinkinasa C antagonisté a inhibitory metabolismus MeSH
- reperfuzní poškození myokardu metabolismus MeSH
- srdeční frekvence MeSH
- srdeční komory enzymologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- inhibitory enzymů MeSH
- Prkcd protein, rat MeSH Prohlížeč
- Prkce protein, rat MeSH Prohlížeč
- proteinkinasa C-delta MeSH
- proteinkinasa C-epsilon MeSH
- proteinkinasa 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.
Citace poskytuje Crossref.org
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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