Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/91347
Type: Artigo de periódico
Title: Potent Cardioprotective Effect Of The 4-anilinoquinazoline Derivative Pd153035: Involvement Of Mitochondrial Katp Channel Activation
Author: Cavalheiro R.A.
Marin R.M.
Rocco S.A.
Cerqueira F.M.
da Silva C.C.C.
Rittner R.
Kowaltowski A.J.
Vercesi A.E.
Franchini K.G.
Castilho R.F.
Abstract: Background: The aim of the present study was to evaluate the protective effects of the 4-anilinoquinazoline derivative PD153035 on cardiac ischemia/reperfusion and mitochondrial function. Methodology/Principal Findings: Perfused rat hearts and cardiac HL-1 cells were used to determine cardioprotective effects of PD153035. Isolated rat heart mitochondria were studied to uncover mechanisms of cardioprotection. Nanomolar doses of PD153035 strongly protect against heart and cardiomyocyte damage induced by ischemia/reperfusion and cyanide/aglycemia. PD153035 did not alter oxidative phosphorylation, nor directly prevent Ca2+ induced mitochondrial membrane permeability transition. The protective effect of PD153035 on HL-1 cells was also independent of AKT phosphorylation state. Interestingly, PD153035 activated K+ transport in isolated mitochondria, in a manner prevented by ATP and 5-hydroxydecanoate, inhibitors of mitochondrial ATP-sensitive K+ channels (mitoKATP). 5-Hydroxydecanoate also inhibited the cardioprotective effect of PD153035 in cardiac HL-1 cells, demonstrating that this protection is dependent on mitoKATP activation. Conclusions/Significance: We conclude that PD153035 is a potent cardioprotective compound and acts in a mechanism involving mitoKATP activation. © 2010 Cavalheiro et al.
Editor: 
Rights: aberto
Identifier DOI: 10.1371/journal.pone.0010666
Address: http://www.scopus.com/inward/record.url?eid=2-s2.0-77956273131&partnerID=40&md5=1e66b81cd636b3a04b816e9ffc9d5788
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

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