Efeito do derivado quinazolinico PD153035 sobre a função mitocondrial : implicações na cardioproteção / Effect of the 4-anilinoquinazoline PD153035 on mitochondrial function : implication in cardioprotection

AUTOR(ES)

Renata Alves Cavalheiro

DATA DE PUBLICAÇÃO

2008

RESUMO

The action of the aminoquinazoline PD153035 on the mitochondrial functions was investigated. The addition of various PD153035 concentrations (5, 10, 20 and 40 μM) to liver mitochondria decreased the mitochondrial respiratory control, induced mitochondrial permeability transition cyclosporin A-sensitive, increased the mitochondrial calcium uptake capacity and reduced mitochondrial reactive oxygen species production. Under this same experimental conditions, no effect was observed in rat heart mitochondria when the rat was treated or not with PD153035 (32 mg/kg v.o.) No effect was also observed in the mitochondrial respiratory control of controls and PD153035-treated animals submitted to ischemia/reperfusion. A rapid rat heart mitochondrial swelling was observed when the mitochondrial suspensions were previously incubated in a hyposmotic solution containing potassium ions while no effect was observed when all K+ of the medium were replaced by sodium or lithium ions. Similar results were observed in isolated rat heart mitochondria incubated in vitro with PD153035 (10 nM). This mitochondrial swelling induced by PD153035 in vivo and in vitro was inhibited by ATP or 5-hydroxydecanoate, both mitoKATP channel antagonists. A smaller rat liver mitochondrial inner membrane potential was observed after PD153035 treatment and this effect was due to ATP hydrolysis by FoF1 ATPase. In addition, cardiac muscle fibers from PD153035-treated rats presented a slight increase in basal respiration supporting the higher mitochondrial K+ permeability. Cardiac cells (HL-1) treated with PD153035 and submitted to a transitory treatment with potassium cyanide in the absence of glucose maintained the cellular viability that was abolished by 5HD. These results suggest that the cardioprotection conferred by the PD153035 probably was related with the mitoKATP activation, since the mitoKATP channel antagonist 5HD inhibited the PD153035 effect on both cardiac mitochondrial K+ permeability and HL-1 cell viability.

ASSUNTO(S)

mitocondria mitochondria

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