Vercesi A E, Bernardes C F, Hoffmann M E, Gadelha F R, Docampo R
Department of Veterinary Pathobiology, University of Illinois, Urbana 61801.
J Biol Chem. 1991 Aug 5;266(22):14431-4.
Digitonin can be used to permeabilize selectively the plasma membrane of Trypanosoma cruzi epimastigotes without significantly affecting the functional integrity of mitochondria. Addition of digitonin at concentrations close to 64 microM caused decrease in the rate of basal respiration of epimastigotes similar to that caused by oligomycin. A further addition of carbonyl cyanide p-trifluorophenylhydrazone (FCCP) brought respiration to the same rate observed prior to the inclusion of digitonin or oligomycin. This suggests that like oligomycin, digitonin is shifting respiration to a nonphosphorylating state probably by depleting the cells from adenine nucleotides due to permeabilization of the plasma membrane. The use of low concentrations of digitonin allowed the quantitative determination of the mitochondrial membrane potential of these cells in situ using safranine O. The response of epimastigotes mitochondrial membrane potential to phosphate, FCCP, valinomycin, nigericin, ADP, and Ca2+ indicates that these mitochondria behave similarly to vertebrate mitochondria regarding the properties of their electrochemical proton gradient. In addition, T. cruzi mitochondria are able to build up and retain a membrane potential of a value comparable to that of mammalian mitochondria. The trypanocidal drug crystal violet, as well as other cationic drugs such as dequalinium, induced a rapid dose-related collapse of the inner mitochondrial membrane potential.
洋地黄皂苷可用于选择性地使克氏锥虫前鞭毛体的质膜通透化,而不会显著影响线粒体的功能完整性。添加浓度接近64微摩尔的洋地黄皂苷会导致前鞭毛体基础呼吸速率降低,类似于寡霉素所引起的降低。进一步添加羰基氰化物对三氟甲氧基苯腙(FCCP)可使呼吸速率恢复到加入洋地黄皂苷或寡霉素之前所观察到的相同水平。这表明,与寡霉素一样,洋地黄皂苷可能是通过质膜通透化使细胞内腺嘌呤核苷酸耗竭,从而将呼吸转变为非磷酸化状态。使用低浓度的洋地黄皂苷能够利用番红O原位定量测定这些细胞的线粒体膜电位。前鞭毛体线粒体膜电位对磷酸盐、FCCP、缬氨霉素、尼日利亚菌素、ADP和Ca2+的反应表明,这些线粒体在其电化学质子梯度特性方面与脊椎动物线粒体表现相似。此外,克氏锥虫线粒体能够建立并维持与哺乳动物线粒体相当的膜电位值。杀锥虫药物结晶紫以及其他阳离子药物如地喹氯铵,可诱导线粒体内膜电位迅速出现剂量相关的崩溃。