期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 14, 期 1, 页码 1-8出版社
ELSEVIER
DOI: 10.1016/j.intimp.2012.05.020
关键词
Holothurians; Triterpene glycosides; Biomembranes; Immune cells
资金
- RFBR [11-04-01084-a]
- FEBRAS [09-II-YO-05-002, 12-III-B-05-070]
The in vitro interactions between triterpene glycoside, cucumarioside A(2)-2, isolated from the Far-Eastern holothurian Cucumaria japonica, and mouse splenocyte and peritoneal macrophage biomembranes were studied. Multiple experimental approaches were employed, including determination of biomembrane microviscosity, membrane potential and Ca2+ signaling, and radioligand binding assays. Cucumarioside A(2)-2 exhibited strong cytotoxic effect in the micromolar range of concentrations and showed pronounced immunomodulatory activity in the nanomolar concentration range. It was established that the cucumarioside A(2)-2 effectively interacted with immune cells and increased the cellular biomembrane microviscosity. This interaction led to a dose-dependent reversible shift in cellular membrane potential and temporary biomembrane depolarization; and an increase in [Ca2+](i) in the cytoplasm. It is suggested that there are at least two binding sites for [H-3]-cucumarioside A(2)-2 on cellular membranes corresponding to different biomembrane components: a low affinity site match to membrane cholesterol that is responsible for the cytotoxic properties, and a high affinity site corresponding to a hypothetical receptor that is responsible for immunostimulation. (C) 2012 Elsevier B.V. All rights reserved.
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