Interaction of holothurian triterpene glycoside with biomembranes of mouse immune cells.
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 Ca(2+) 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 [Ca(2+)](i) in the cytoplasm. It is suggested that there are at least two binding sites for [(3)H]-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.
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far East Division of the Russian Academy of Sciences, Vladivostok, 690022, Russia. pislyagin@hotmail.com
E A
EA
Pislyagin
R V
RV
Gladkikh
I I
II
Kapustina
N Yu
NY
Kim
V P
VP
Shevchenko
I Yu
IY
Nagaev
S A
SA
Avilov
D L
DL
Aminin
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D048016:Cucumaria / Q000276:immunology*; D005260:Female; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D056747:Immunomodulation; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000648:ultrastructure; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013154:Spleen / Q000378:metabolism / Q000648:ultrastructure; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014783:Viscosity / Q000187:drug effects
D006027:Glycosides; D012503:Saponins; D014315:Triterpenes; C539161:cucumarioside A2-2