Temporal Changes in Myocardial Salvage Kinases During Reperfusion Following Ischemia : Studies Involving the Cardioprotective Adipocytokine Apelin

• Published in: Cardiovascular drugs and therapy Vol. 21; no. 6; pp. 409 - 414
• Main Authors: SMITH, Christopher C. T, MOCANU, Michaela M, BOWEN, Jonathan, WYNNE, Abigail M, SIMPKIN, James C, DIXON, Richard A, COOPER, Michael B, YELLON, Derek M
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.12.2007; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular system; Enzyme-linked immunosorbent assay; Extracellular Signal-Regulated MAP Kinases - metabolism; Health risks; Intercellular Signaling Peptides and Proteins - pharmacology; Ischemia; Kinases; Male; MAP kinase; Medical sciences; Mice; Mice, Inbred C57BL; Myocardial Ischemia - enzymology; Myocardial Reperfusion Injury - enzymology; Myocardial Reperfusion Injury - prevention & control; Myocardium - enzymology; Pharmacology. Drug treatments; Phosphorylation; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Reperfusion; Threonine; Western blotting; ischemia-reperfusion injury; Reperfusion; Enzyme; Kinase; Transferases; Ischemia reperfusion; Cardioprotective agent; salvage kinases; Myocardium; temporal changes; Circulatory system; Change
• ISSN: 0920-3206; 1573-7241
• DOI: 10.1007/s10557-007-6054-y

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. 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). 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. 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.