We previously showed that endogenous or exogenous PAF can precondition the rat heart. Here, we investigated the molecular mechanisms involved in PAF-induced cardioprotection against ischemia/reperfusion injury. In Group 1 control hearts, isolated rat hearts underwent 30-minutes global ischemia and 2-hours of reperfusion; Group 2) hearts were perfused for 19-min with PAF (2 × 10− 11 M) before ischemia; Groups 3 and 4) before the ischemia hearts underwent co-infusion either with PAF and N-acetyl-L-cysteine or PAF and 5-hydroxydecanoate to scavenge ROS or to block mitochondrial-ATP-sensitive K+ (mKATP) channels, respec- tively. Group 5) in PAF-pretreated hearts, Atractyloside, an opener of mitochondrial permeability transition pore (mPTP), was infused during the initial 20 min of reperfusion. 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 post-ischemic left ventricular function. PAF beneficial effects were abolished by N-acetyl-L-cysteine, 5-hydroxydecanoate or Atractyloside. PAF-pretreatment up-regulated phosphorylation/ activation of protein kinases (PKCe and PKB/Akt) both in the pre- and post-ischemic period, and the phosphorylation/inactivation of glycogen synthase kinase-3β (GSK-3β) at reperfusion. Thus, PAF- protective cascade requires both a pre-ischemic mKATP channels and redox signaling activation and a post -ischemi c PKB/Akt activation, GSK-3β inhibition and closing of mPTP.

Preconditioning-like effect of the platelet activating factor (PAF): Pre- and post-ischemic signaling pathway in isolated rat hearts / PENNA C; MOGNETTI B; TULLIO F; GATTULLO D; MANCARDI D; ALLOATTI G; PAGLIARO P. - In: COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY. PART A, MOLECULAR & INTEGRATIVE PHYSIOLOGY. - ISSN 1095-6433. - STAMPA. - 150(2008), pp. S128-S128. ((Intervento presentato al convegno Annual Main Meeting of the Society of Experimental Biology tenutosi a Marseille, France nel 2008.

Preconditioning-like effect of the platelet activating factor (PAF): Pre- and post-ischemic signaling pathway in isolated rat hearts

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

Abstract

We previously showed that endogenous or exogenous PAF can precondition the rat heart. Here, we investigated the molecular mechanisms involved in PAF-induced cardioprotection against ischemia/reperfusion injury. In Group 1 control hearts, isolated rat hearts underwent 30-minutes global ischemia and 2-hours of reperfusion; Group 2) hearts were perfused for 19-min with PAF (2 × 10− 11 M) before ischemia; Groups 3 and 4) before the ischemia hearts underwent co-infusion either with PAF and N-acetyl-L-cysteine or PAF and 5-hydroxydecanoate to scavenge ROS or to block mitochondrial-ATP-sensitive K+ (mKATP) channels, respec- tively. Group 5) in PAF-pretreated hearts, Atractyloside, an opener of mitochondrial permeability transition pore (mPTP), was infused during the initial 20 min of reperfusion. 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 post-ischemic left ventricular function. PAF beneficial effects were abolished by N-acetyl-L-cysteine, 5-hydroxydecanoate or Atractyloside. PAF-pretreatment up-regulated phosphorylation/ activation of protein kinases (PKCe and PKB/Akt) both in the pre- and post-ischemic period, and the phosphorylation/inactivation of glycogen synthase kinase-3β (GSK-3β) at reperfusion. Thus, PAF- protective cascade requires both a pre-ischemic mKATP channels and redox signaling activation and a post -ischemi c PKB/Akt activation, GSK-3β inhibition and closing of mPTP.
Annual Main Meeting of the Society of Experimental Biology
Marseille, France
2008
150
S128
S128
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY. PART A, MOLECULAR & INTEGRATIVE PHYSIOLOGY
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/2318/130664
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