Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/198871
Type: Artigo de periódico
Title: Potent Cardioprotective Effect Of The 4-anilinoquinazoline Derivative Pd153035: Involvement Of Mitochondrial K(atp) Channel Activation.
Author: Cavalheiro, Renata A
Marin, Rodrigo M
Rocco, Silvana A
Cerqueira, Fernanda M
da Silva, Camille C Caldeira
Rittner, Roberto
Kowaltowski, Alicia J
Vercesi, Anibal E
Franchini, Kleber G
Castilho, Roger F
Abstract: 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. 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 Ca(2+) 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 (mitoK(ATP)). 5-Hydroxydecanoate also inhibited the cardioprotective effect of PD153035 in cardiac HL-1 cells, demonstrating that this protection is dependent on mitoK(ATP) activation. We conclude that PD153035 is a potent cardioprotective compound and acts in a mechanism involving mitoK(ATP) activation.
Subject: Adenosine Triphosphate
Animals
Biological Transport
Calcium
Cardiotonic Agents
Cell Respiration
Cyanides
Heart Function Tests
In Vitro Techniques
Ion Channel Gating
Male
Mice
Mitochondria
Myocardial Reperfusion Injury
Myocardium
Permeability
Phosphorylation
Potassium
Potassium Channels
Proto-oncogene Proteins C-akt
Quinazolines
Rats
Rats, Wistar
Rights: aberto
Identifier DOI: 10.1371/journal.pone.0010666
Address: http://www.ncbi.nlm.nih.gov/pubmed/20498724
Date Issue: 2010
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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