Temporal changes in myocardial salvage kinases during reperfusion following ischemia: studies involving the cardioprotective adipocytokine apelin.

Abstract

INTRODUCTION:

Activation of the Reperfusion Injury Salvage Kinase (RISK) pathway, which incorporates phosphatidylinositol-3-OH kinase (PI3K)-Akt/protein kinase B (PKB) and p44/42 mitogen-activated protein kinase (MAPK), underlies protection against ischemia-reperfusion (I/R) injury. The temporal nature of the activation of these RISK pathway components during reperfusion is, however, uncertain. We examined Akt and p44/42 phosphorylation in hearts subjected to ischemia and varying periods of reperfusion in the absence or presence of the putative cardioprotectant, apelin-13. Akt activity was also measured.

MATERIALS AND METHODS:

Langendorff perfused C57Bl/6J mouse hearts were subjected to 35 min global ischemia followed by 0, 2.5, 5 or 10 min reperfusion with or without 1 microM apelin-13. Basal and apelin-induced phosphorylation of Akt (at both the threonine 308 and serine 473 phosphorylation sites) and p44/42 during the reperfusion phase was determined by Western blotting and Akt activity measured using an Enzyme-Linked ImmunoSorbent Assay (ELISA).

RESULTS:

Basal phosphorylation of both Akt and p44/42 increased progressively with time of reperfusion. Apelin enhanced Akt and p44/42 phosphorylation at all reperfusion time points. Akt activity did not change under basal conditions but was increased by apelin at 5 min (NS) and 10 min (p<0.05) reperfusion.

DISCUSSION:

We conclude that under basal conditions Akt and p44/42 phosphorylation increases with time of reperfusion but that this is not accompanied by increased kinase (Akt) activity. On application of a cardioprotectant, however, kinase phosphorylation and activity are enhanced suggesting that it is the combination of these two mechanisms that may underly the tissue preserving actions of such agents.

• Authors: Christopher C T Smith, Michaela M Mocanu, Jonathan Bowen, Abigail M Wynne, James C Simpkin, Richard A Dixon, Michael B Cooper, Derek M Yellon
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 21 Issue 6 Pg. 409-14 (Dec 2007) ISSN: 0920-3206 [Print] United States
• PMID: 17924178 (Publication Type: Journal Article)

Chemical References

• Intercellular Signaling Peptides and Proteins
• apelin-13 peptide
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Intercellular Signaling Peptides and Proteins (pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Myocardial Ischemia (enzymology)
• Myocardial Reperfusion Injury (enzymology, prevention & control)
• Myocardium (enzymology)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)