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Dodecyltriphenylphosphonium As an Inducer of Potassium-Dependent Permeability in Rat Liver Mitochondria
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology ( IF 1.1 ) Pub Date : 2019-10-01 , DOI: 10.1134/s1990747819040044
K. N. Belosludtsev , K. S. Tenkov , A. A. Vedernikov , N. V. Belosludtseva , M. V. Dubinin

Dodecyltriphenylphosphonium (C12TPP) is a membrane-bound penetrating cation with a delocalized charge widely used for creating and delivering of antioxidants, spin traps, and other chemical probes into mitochondria. The ability of C12TPP to induce permeabilization of the inner membrane of rat liver mitochondria at micromolar concentrations was investigated. It was found that C12TPP in a dose-dependent manner (10–30 µM) caused swelling of rat liver mitochondria in the incubation medium, the osmolarity of which was maintained with KCl. At the same time, C12TPP induced the reduction of the volume of rat liver mitochondria in the isotonic sucrose medium. It was shown that mitochondrial swelling induced by C12TPP was not inhibited by cyclosporin A, but it was suppressed by glibenclamide and ATP, the inhibitors of the ATP-sensitive potassium channel. It was also found that the C12TPP-induced mitochondrial swelling was inhibited by free saturated fatty acids. In turn, C12TPP prevented mitochondrial swelling induced by palmitic acid and Ca2+, which was insensitive to cyclosporin A. A possible mechanism of the C12TPP-induced permeabilization of the inner mitochondrial membrane is discussed.

中文翻译:

十二烷基三苯基鏻作为大鼠肝脏线粒体中钾依赖性渗透性的诱导剂

十二烷基三苯基鏻 (C12TPP) 是一种膜结合的穿透阳离子,具有离域电荷,广泛用于产生和递送抗氧化剂、自旋陷阱和其他化学探针进入线粒体。研究了 C12TPP 在微摩尔浓度下诱导大鼠肝线粒体内膜透化的能力。发现 C12TPP 以剂量依赖性方式(10-30 µM)导致培养介质中大鼠肝线粒体肿胀,其渗透压用 KCl 维持。同时,C12TPP在等渗蔗糖培养基中诱导大鼠肝线粒体体积减少。结果表明,C12TPP 诱导的线粒体肿胀不受环孢菌素 A 的抑制,但可被格列本脲和 ATP(ATP 敏感性钾通道的抑制剂)抑制。还发现游离饱和脂肪酸抑制了 C12TPP 诱导的线粒体肿胀。反过来,C12TPP 可防止由棕榈酸和 Ca2+ 诱导的线粒体肿胀,而后者对环孢菌素 A 不敏感。讨论了 C12TPP 诱导的线粒体内膜透化的可能机制。
更新日期:2019-10-01
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