Incorporation of pentacyclic triterpenes into mitochondrial membrane--studies on the interactions in model 2D lipid systems.

Abstract

Three representatives of naturally occurring pentacyclic triterpenes (PTs) were subjected to comprehensive studies aimed at the analysis of their interactions with phospholipids found naturally in mitochondrial membrane. To reach this goal, the selected compounds--α-amyrin (AMalf), betulinic acid (BAc), and ursolic acid (Urs)--were incorporated into two-component and multicomponent Langmuir monolayers acting as a model of mitochondrial membrane. As the lipids characteristic for mitochondria, phosphatidylcholine (POPC), phosphatidylethanolamine (POPE), and cardiolipin (BHCL) were chosen. Our studies were motivated by the fact that, according to the literature, the anticancer activity of PTs is correlated with their ability to incorporate into mitochondrial membrane and modify its properties. The undertaken studies were based on the surface pressure (π)-molecular area (A) isotherm registration complemented with the thermodynamic analysis and BAM visualization. It was found that all three terpenes with the exception of high betulinic acid proportion (30 and 50%) interact beneficially with POPC in two-component monolayers, while incorporation of BAc and Urs into POPE film is energetically unfavorable. As far as the model mitochondrial membrane composed of POPC/POPE/BHCL is concerned, the largest destructive influence (high positive values of ΔG(Exc) and decrease of the model monolayer condensation) was found in the case of terpene acids, while the effect of α-amyrin was energetically favorable. We postulated that the origin of the observed findings is connected with the specific interactions between bolaamphlilic terpene acids and POPE, known from its propensity to form intermolecular hydrogen bonds.