Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Biomedical Research Center, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Int J Mol Sci. 2024 May 30;25(11):6026. doi: 10.3390/ijms25116026.
In our previous study, two oleanane-type pentacyclic triterpenoids (oleanolic acid and maslinic acid) were reported to affect the -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 -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 ,-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 -glycosylation without affecting the cell surface expression of the ICAM-1 protein. In contrast, -boswellic acid and maslinic acid interfered with the -glycosylation of the ICAM-1 protein, which resulted in the accumulation of high-mannose-type -glycans. Among the oleanane-type triterpenoids tested, -boswellic acid and maslinic acid uniquely interfered with the intracellular trafficking and -glycosylation of glycoproteins.
在我们之前的研究中，两种齐墩果烷型五环三萜（齐墩果酸和马桑酸）被报道影响细胞间黏附分子-1（ICAM-1）的 -糖基化和细胞内运输。本研究旨在研究 13 种齐墩果烷型天然三萜的构效关系，探讨其对核因子 κB（NF-κB）信号通路以及人肺腺癌细胞 A549 中 ICAM-1 蛋白的表达、细胞内运输和 -糖基化的影响。具有两个羟基的熊果酸、羽扇豆酸、赤藓醇和马桑酸降低了 A549 细胞的活力。具有,-不饱和羰基的雷公藤红素和普瑞巴林降低了细胞活力，但更强烈地抑制了白细胞介素-1α诱导的 NF-κB 信号通路。齐墩果酸、莫诺酸和甘草次酸干扰 -糖基化而不影响 ICAM-1 蛋白的细胞表面表达。相比之下， -乳香酸和马桑酸干扰了 ICAM-1 蛋白的 -糖基化，导致高甘露糖型 -聚糖的积累。在测试的齐墩果烷型三萜中， -乳香酸和马桑酸独特地干扰了糖蛋白的细胞内运输和 -糖基化。
