Up-regulation and redistribution of protein kinase C-δ in chronically hypoxic heart

Markéta Hlaváčková1, Kristýna Kožichová, Jan Neckář

  • 1Department of Cell Biology, Faculty of Science, Charles University in Prague, Vinicna 7, 128 00, Prague 2, Czech Republic. hlavacko@natur.cuni.cz

Insights

Chronic intermittent hypoxia (CIH) up-regulates protein kinase C-delta (PKC-δ) in rat hearts, localizing it to mitochondria and sarcolemma. This PKC-δ isoform plays a key role in CIH-induced cardiac protection against injury.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • Cellular Adaptation

Background:

  • Chronic hypoxia confers cardiac protection against ischemia-reperfusion injury.
  • Protein kinase C (PKC) isoforms are implicated in cardioprotection, but their specific roles are unclear.
  • Understanding PKC isoform involvement is crucial for developing therapeutic strategies.

Purpose of the Study:

  • To investigate the effects of chronic intermittent hypoxia (CIH) on PKC-δ and PKC-ε expression and localization.
  • To examine the impact of a PKC-δ inhibitor (rottlerin) on these changes.
  • To elucidate the role of PKC-δ in CIH-induced cardiac adaptation.

Main Methods:

  • Adult male Wistar rats were exposed to CIH (7,000 m, 8 h/day).
  • PKC-δ and PKC-ε levels and phosphorylation were assessed using Western blot.
  • Subcellular distribution was analyzed by quantitative immunofluorescence microscopy.
  • Nitrotyrosine formation and oxidative phosphorylation complexes were evaluated.

Main Results:

  • CIH increased total and phosphorylated PKC-δ levels, with enhanced mitochondrial and sarcolemmal localization.
  • CIH decreased total PKC-ε but did not affect its phosphorylation.
  • Rottlerin partially reversed CIH-induced PKC-δ redistribution and reduced nitrotyrosine formation.
  • CIH led to a slight decrease in oxidative phosphorylation complexes, primarily complex II.

Conclusions:

  • Up-regulated PKC-δ, localized to mitochondrial and sarcolemmal membranes, is a key player in CIH-induced cardiac ischemic tolerance.
  • Inhibiting PKC-δ with rottlerin affects its subcellular redistribution and offers cardioprotection.
  • These findings highlight PKC-δ as a potential therapeutic target for enhancing cardiac resilience.

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