We previously showed that endogenous platelet activating factor (PAF) is involved in heart preconditioning. We studied the intracellular pathways involved in PAF-induced cardioprotection. In Group 1 control hearts, Langendorff-perfused rat hearts underwent 30 minutes ischemia and 2 hours of reperfusion. Group 2 hearts, before ischemia, were perfused for 19 min with PAF (2x10–11 M); Groups 3 and 4 hearts were co-infused with PAF and N-acetyl-L-cysteine or 5-hydroxydecanoate to scavenge ROS or to block mitochondrial-ATP-sensitive K+ (mKATP) channels, respectively. In Group 5, PAF pretreated hearts were infused during the initial 20 min of reperfusion with Atractyloside, a mitochondrial permeability transition pore (mPTP) opener. Left ventricular pressure and infarct size were determined. In sixteen additional hearts the phosphorylation of kinases by PAF was determined both in pre- and post-ischemic period. PAF-pretreatment reduced infarct size (33±4% vs 64±4.6 % of the area at risk of control hearts) and improved pressure recovery. Infarct-sparing effect of PAF was abolished by N-acetyl-L-cysteine, 5-hydroxydecanoate and Atractyloside. PAF-pretreatment enhanced the phosphorylation/activation of protein kinases (PKCε and PKB/Akt) both in the pre- and post-ischemic period, and preserved the phosphorylation/inactivation of glycogen synthase kinase-3β (GSK-3β) in reperfusion. Thus, PAF-pretreatment involves activation of mKATP channels and redox signaling in pre-ischemic phase, and PKB/Akt activation, GSK-3β inhibition and closing of mPTP in reperfusion, which explain cardioprotection.

Preconditioning-like cardioprotective effect of the platelet-activating factor: pre- and post-ischemic signaling pathway / PENNA C; MOGNETTI B; TULLIO F; GATTULLO D; MANCARDI D; ALLOATTI G; PAGLIARO P. - In: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY. - ISSN 0022-2828. - STAMPA. - 44:4(2008), pp. S270-S270. ((Intervento presentato al convegno XXVIII Annual Meeting European Section of the International Society for Heart Research tenutosi a Atene nel 2008.

Preconditioning-like cardioprotective effect of the platelet-activating factor: pre- and post-ischemic signaling pathway

PENNA, Claudia;MOGNETTI, Barbara;TULLIO, FRANCESCA;MANCARDI, Daniele;ALLOATTI, Giuseppe;PAGLIARO, Pasquale
2008

Abstract

We previously showed that endogenous platelet activating factor (PAF) is involved in heart preconditioning. We studied the intracellular pathways involved in PAF-induced cardioprotection. In Group 1 control hearts, Langendorff-perfused rat hearts underwent 30 minutes ischemia and 2 hours of reperfusion. Group 2 hearts, before ischemia, were perfused for 19 min with PAF (2x10–11 M); Groups 3 and 4 hearts were co-infused with PAF and N-acetyl-L-cysteine or 5-hydroxydecanoate to scavenge ROS or to block mitochondrial-ATP-sensitive K+ (mKATP) channels, respectively. In Group 5, PAF pretreated hearts were infused during the initial 20 min of reperfusion with Atractyloside, a mitochondrial permeability transition pore (mPTP) opener. Left ventricular pressure and infarct size were determined. In sixteen additional hearts the phosphorylation of kinases by PAF was determined both in pre- and post-ischemic period. PAF-pretreatment reduced infarct size (33±4% vs 64±4.6 % of the area at risk of control hearts) and improved pressure recovery. Infarct-sparing effect of PAF was abolished by N-acetyl-L-cysteine, 5-hydroxydecanoate and Atractyloside. PAF-pretreatment enhanced the phosphorylation/activation of protein kinases (PKCε and PKB/Akt) both in the pre- and post-ischemic period, and preserved the phosphorylation/inactivation of glycogen synthase kinase-3β (GSK-3β) in reperfusion. Thus, PAF-pretreatment involves activation of mKATP channels and redox signaling in pre-ischemic phase, and PKB/Akt activation, GSK-3β inhibition and closing of mPTP in reperfusion, which explain cardioprotection.
XXVIII Annual Meeting European Section of the International Society for Heart Research
Atene
2008
44
4
S270
S270
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Heart; Ischemia/reperfusion; Platelet activating factor; Cardioprotection
PENNA C; MOGNETTI B; TULLIO F; GATTULLO D; MANCARDI D; ALLOATTI G; PAGLIARO P
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/128820
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