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Effect of betulin and betulonic acid on isolated rat liver mitochondria and liposomes.
Biochimica et Biophysica Acta (BBA) - Biomembranes ( IF 3.4 ) Pub Date : 2020-06-06 , DOI: 10.1016/j.bbamem.2020.183383
Mikhail V Dubinin 1 , Alena A Semenova 1 , Anna I Ilzorkina 1 , Irina B Mikheeva 2 , Valery A Yashin 3 , Nikita V Penkov 3 , Valentina A Vydrina 4 , Gumer Yu Ishmuratov 4 , Vyacheslav A Sharapov 1 , Ekaterina I Khoroshavina 1 , Sergey V Gudkov 5 , Konstantin N Belosludtsev 6
Affiliation  

The paper considers the effects of plant triterpenoid betulin and its derivative betulonic acid on rat liver mitochondria and liposomes. It was found that betulonic acid and, to a lesser extent, betulin, activate mitochondrial respiration in states 2 and 4 and inhibit ADP- and DNP-stimulated (uncoupled) respiration. The effect of betulonic acid resulted in a significant decrease of the respiratory control and ADP/O ratios and decrease in Δψ. The effects of both compounds were most pronounced in the case of succinate-fueled mitochondrial respiration. This may include both the possible protonophore effect of betulonic acid and the inhibition of respiratory chain complexes by both compounds. Both agents enhanced H2O2 production in succinate-fueled mitochondria, while betulonic acid exerted an antioxidant effect with NAD-dependent substrates. Betulin was found to induce mitochondrial aggregation, but had no effect on membrane permeability. A similar pattern was found on liposomes. As revealed by the laurdan generalized polarization (GP) technique, betulin increased laurdan GP in lecithin liposomes, indicating a decrease in membrane fluidity. Measurements of GP as a function of fluorescence excitation wavelength gave an ascending line for high concentrations of betulin, which can be interpreted as phase heterogeneity of the lipid/betulin system. High concentrations of betulin (> 60 mol%) was also demonstrated to cause permeabilization of lecithin liposomes. Betulonic acid was much less effective in inducing the aggregation of mitochondria and liposomes and had no effect on membrane permeability. The possible mechanisms of betulin and betulonic acid effect on rat liver mitochondria and liposomes are discussed.



中文翻译:

桦木和桦木酸对离体大鼠肝线粒体和脂质体的影响。

本文考虑了植物三萜类桦木蛋白及其衍生物桦木酸对大鼠肝线粒体和脂质体的影响。已发现,倍他宁酸和(在较小程度上)倍他林可激活状态2和4中的线粒体呼吸,并抑制ADP和DNP刺激的(非耦合)呼吸。倍他宁酸的作用导致呼吸控制和ADP / O比率显着下降,Δψ下降。在琥珀酸刺激的线粒体呼吸作用中,这两种化合物的作用最为明显。这可能既包括可能存在的丁烯二酸质子载体效应,也包括两种化合物对呼吸链复合物的抑制作用。两种试剂均增强了H 2 O 2丁二酸生产的线粒体中产生β-羟色胺,而丁烯二酸对NAD依赖性底物发挥抗氧化作用。发现贝特林诱导线粒体聚集,但对膜通透性没有影响。在脂质体上发现了类似的模式。如laurdan通用极化(GP)技术所揭示的,甜菜碱在卵磷脂脂质体中增加了laurdan GP,表明膜流动性降低。GP作为荧光激发波长的函数的测量给出了高浓度桦木素的上升线,这可以解释为脂质/白蛋白系统的相异质性。高浓度的白桦蛋白(> 60 mol%)也被证明可引起卵磷脂脂质体的透化。乙二酸在诱导线粒体和脂质体聚集方面效果不佳,对膜的通透性没有影响。讨论了桦木和桦木酸对大鼠肝线粒体和脂质体影响的可能机制。

更新日期:2020-06-06
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