Interactions of pentacyclic triterpene acids with cardiolipins and related phosphatidylglycerols in model systems
Interactions of pentacyclic triterpene acids with cardiolipins and related phosphatidylglycerols in model systems
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DOI：
10.1016/j.bbamem.2014.05.027
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发表时间：
2014-10-01
影响因子：
3.4
通讯作者：
Miskowiec, Pawel
中科院分区：
文献类型：
--
作者：
Broniatowski, Marcin;Flasinski, Michal;Miskowiec, Pawel
五环三萜酸（PTA）：桦木酸（BAc）、齐墩果酸（可乐）和熊果酸（Urs）是用于治疗癌症和细菌感染的有效药物。 PTA 作用机制是多因素的，但重要的一步是它们与线粒体和细菌膜脂质的相互作用。在我们的研究中，我们应用 Langmuir 单层技术来研究 PTA 与心磷脂 (CL) 和磷脂酰甘油 (PG) 之间的相互作用。我们应用了两种不同的哺乳动物线粒体 CL 和一种从大肠杆菌膜中提取的物种。为了进行比较，我们对包含 PTA 和 3 个 PG 的系统进行了相同的实验，这些 PG 与所应用的 CL 结构严格相关。我们的研究证明，PTAs 可以通过与磷脂酰甘油的相互作用扰乱富含 CL 结构域的组织并影响细菌膜的流动性，因此阴离子磷脂是其膜作用的目标。结果的热力学解释表明，Urs 在 3 个研究的 PTA 中具有最高的膜解组织潜力。对模型系统进行的研究还证明，BAc 可以区分结构相似的动物心磷脂种类，与 BHCL（主要的哺乳动物 CL）特异性相互作用，并可以扰乱其在膜中的组织。相比之下，Ola 和 Urs 在与细菌 as 和 PG 的相互作用方面非常活跃。 (C) 2014 Elsevier B.V. 保留所有权利。
Pentacyclic triterpene acids (PTAs): betulinic (BAc), oleanolic Cola) and ursolic (Urs) are potent pharmaceuticals applied in the therapy of cancer and bacterial infections. The mechanism of PTA action is multifactor, but the important step is their interaction with the lipids of mitochondrial and bacterial membranes. In our studies we applied the Langmuir monolayer technique to investigate the interactions between PTAs and cardiolipins (CLs) and phosphatidylglycerols (PGs). We applied two different mammalian mitochondrial CLs and one species extracted from the membrane of Escherichia coli. For comparison we performed the same experiments on the systems containing PTAs and 3 PGs strictly correlated structurally to the applied CLs. Our studies proved that PTAs can disturb the organization of CL-rich domains and affect the bacterial membrane fluidity by the interactions with phosphatidylglycerols, so anionic phospholipids are the targets of their membrane action. The thermodynamic interpretation of the results indicated that Urs has the highest membrane disorganizing potential among the 3 studied PTAs. The studies performed on model systems proved also that BAc can discriminate over structurally similar animal cardiolipin species, interacts specifically with BHCL - the main mammalian CL and can disturb its organization in the membrane. In contrast, Ola and Urs are much active as far as the interaction with bacterial as and PGs is concerned. (C) 2014 Elsevier B.V. All rights reserved.