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Post-ischaemic activation of kinases in the pre-conditioning-like cardioprotective effect of the platelet-activating factor

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Abstract:

Abstract Aim: 

Platelet-activating factor (PAF) triggers cardiac pre-conditioning against ischemia/reperfusion injury. The actual protection of ischaemic pre-conditioning occurs in the reperfusion phase. Therefore, we studied in this phase the kinases involved in PAF-induced pre-conditioning. Methods: 

Langendorff-perfused rat hearts underwent 30 min of ischaemia and 2 h of reperfusion (group 1, control). Before ischaemia, group 2 hearts were perfused for 19 min with PAF (2 × 10−11 m); groups 3–5 hearts were co-infused during the initial 20 min of reperfusion, with the protein kinase C (PKC) inhibitor chelerythrine (5 × 10−6 m) or the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (5 × 10−5 m) and atractyloside (2 × 10−5 m), a mitochondrial permeability transition pore (mPTP) opener respectively. Phosphorylation of PKCε, PKB/Aκt, GSK-3β and ERK1/2 at the beginning of reperfusion was also checked. Left ventricular pressure and infarct size were determined. Results: 

PAF pre-treatment reduced infarct size (33 ± 4% vs. 64 ± 5% of the area at risk of control hearts) and improved pressure recovery. PAF pre-treatment enhanced the phosphorylation/activation of PKCε, PKB/Aκt and the phosphorylation/inactivation of GSK-3β at reperfusion. Effects on ERK1/2 phosphorylation were not consistent. Infarct-sparing effect and post-ischaemic functional improvement induced by PAF pre-treatment were abolished by post-ischaemic infusion of either chelerythrine, LY294002 or atractyloside. Conclusions: 

The cardioprotective effect exerted by PAF pre-treatment involves activation of PKC and PI3K in post-ischaemic phases and might be mediated by the prevention of mPTP opening in reperfusion via GSK-3β inactivation.

Keywords: infarct size; phosphoinositide 3-kinase; protein kinase C; reperfusion injury

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1748-1716.2009.02000.x

Affiliations:  Laboratories of Physiology and Pharmacology, Department of Clinical and Biological Sciences, University of Torino, Torino, Italy

Publication date: November 1, 2009

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