在我们之前的研究中,据报道,两种齐墩果型五环三萜类化合物(齐墩果酸和山楂酸)会影响细胞间粘附分子1(ICAM-1)的N-糖基化和细胞内运输。本研究旨在研究13种齐墩果类天然三萜类化合物与核因子κB(NF-κB)信号通路的构效关系及其表达,细胞内贩运,和人肺腺癌A549细胞中ICAM-1蛋白的N-糖基化。Hederagenin,棘突酸,赤二醇,和山楂酸,都有两个羟基,降低了A549细胞的活力。雷公藤多和pristiterin,两者都具有α,β-不饱和羰基,降低细胞活力,但更强烈地抑制白细胞介素-1α诱导的NF-κB信号通路。齐墩果酸,吗啡酸,和甘草次酸干扰N-糖基化而不影响ICAM-1蛋白的细胞表面表达。相比之下,α-乳香酸和山楂酸干扰了ICAM-1蛋白的N-糖基化,导致高甘露糖型N-聚糖的积累。在测试的齐墩果类三萜类化合物中,α-乳香酸和山楂酸独特地干扰了糖蛋白的细胞内运输和N-糖基化。
In our previous study, two oleanane-type pentacyclic triterpenoids (oleanolic acid and maslinic acid) were reported to affect the N-glycosylation and intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1). The present study was aimed at investigating the structure-activity relationship of 13 oleanane-type natural triterpenoids with respect to the nuclear factor κB (NF-κB) signaling pathway and the expression, intracellular trafficking, and N-glycosylation of the ICAM-1 protein in human lung adenocarcinoma A549 cells. Hederagenin, echinocystic acid, erythrodiol, and maslinic acid, which all possess two hydroxyl groups, decreased the viability of A549 cells. Celastrol and pristimerin, both of which possess an α,β-unsaturated carbonyl group, decreased cell viability but more strongly inhibited the interleukin-1α-induced NF-κB signaling pathway. Oleanolic acid, moronic acid, and glycyrrhetinic acid interfered with N-glycosylation without affecting the cell surface expression of the ICAM-1 protein. In contrast, α-boswellic acid and maslinic acid interfered with the N-glycosylation of the ICAM-1 protein, which resulted in the accumulation of high-mannose-type N-glycans. Among the oleanane-type triterpenoids tested, α-boswellic acid and maslinic acid uniquely interfered with the intracellular trafficking and N-glycosylation of glycoproteins.