Preconditioning tachycardia decreases the activity of the mitochondrial permeability transition pore in the dog heart

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• 作者：Gina S&#xe1 ; nchez^a ; ^b ; ^{gisanchez@med.uchile.cl" rel="nofollow} ; ^{ginaluisa.sanchez@gmail.com" rel="nofollow} ; Carolina Fern&#xe1 ; ndez^a ; Luis Montecinos^a ; Raú ; l J. Domenech^a ; Paulina Donoso^a ; ^b
• 关键词：Cardioprotection ; Preconditioning ; Cyclophilin-D ; Mitochondrial swelling ; S-glutathionylation ; Protein redox modification
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2011
• 出版时间：15 July 2011
• 年：2011
• 卷：410
• 期：4
• 页码：916-921
• 全文大小：364 K

文摘

Cardioprotection by preconditioning is a central issue of current research on heart function. Several reports indicate that preventing the assembly and opening of the mitochondrial permeability transition pore (mPTP) protects the heart against ischemia–reperfusion injury. We have previously reported that brief episodes of tachycardia decrease the infarct size produced by subsequent prolonged occlusion of a coronary artery, indicating that controlled tachycardia is an effective preconditioning manoeuvre. The effects of preconditioning tachycardia on mPTP activity have not been reported. Therefore, in this work we investigated if preconditioning tachycardia protects against calcium-induced mitochondrial swelling, a measure of mPTP activity. We found that tachycardia decreased by 2.5-fold the rate of mitochondrial calcium-induced swelling, a factor that presumably contributes to the cardioprotective effects of tachycardia. The oxidative status of the cell increased after tachycardia, as evidenced by the decrease in the cellular and mitochondrial GSH/GSSG ratio. We also observed increased S-glutathionylation of cyclophilin-D, an essential mPTP component, after tachycardia. This reversible redox modification of cyclophilin-D may account, al least in part, for the decreased mPTP activity produced by preconditioning tachycardia.