The effect of valinomycin in fibroblasts from patients with fatty acid oxidation disorders

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• 作者：Uzochi Chimdinma Ndukwe Erlingsson ; Francesco Iacobazzi ; Aiping Liu ; Orly Ardon ; Marzia Pasquali ; Nicola Longo
• 关键词：Fatty acid oxidation ; Valinomycin ; Carnitine ; Very long chain acyl CoA dehydrogenase deficiency
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2013
• 出版时间：9 August, 2013
• 年：2013
• 卷：437
• 期：4
• 页码：637-641
• 全文大小：494 K

文摘

Disorders of the carnitine cycle and of the beta oxidation spiral impair the ability to obtain energy from fats at time of fasting and stress. This can result in hypoketotic hypoglycemia, cardiomyopathy, cardiac arrhythmia and other chronic medical problems. The in vitro study of fibroblasts from patients with these conditions is impaired by their limited oxidative capacity. Here we evaluate the capacity of valinomycin, a potassium ionophore that increases mitochondrial respiration, to increase the oxidation of fatty acids in cells from patients with inherited fatty acid oxidation defects. The addition of valinomycin to fibroblasts decreased the accumulation of the lipophilic cation tetraphenylphosphonium (TPP⁺) at low concentrations due to the dissipation of the mitochondrial membrane potential. At higher doses, valinomycin increased TPP⁺ accumulation due to the increased potassium permeability of the plasma membrane and subsequent cellular hyperpolarization. The incubation of normal fibroblasts with valinomycin increased [¹⁴C]-palmitate oxidation (measured as [¹⁴C]O₂ release) in a dose-dependent manner. By contrast, valinomycin failed to increase palmitate oxidation in fibroblasts from patients with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. This was not observed in fibroblasts from patients heterozygous for this condition. These results indicate that valinomycin can increase fatty acid oxidation in normal fibroblasts and could be useful to differentiate heterozygotes from patients affected with VLCAD deficiency.