RESUMEN
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.
Asunto(s)
Membrana Celular/efectos de los fármacos , Cucumaria/inmunología , Glicósidos/farmacología , Saponinas/farmacología , Triterpenos/farmacología , Animales , Señalización del Calcio/efectos de los fármacos , Membrana Celular/química , Membrana Celular/metabolismo , Membrana Celular/ultraestructura , Femenino , Glicósidos/química , Glicósidos/aislamiento & purificación , Inmunomodulación , Macrófagos Peritoneales/metabolismo , Macrófagos Peritoneales/ultraestructura , Potenciales de la Membrana/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Saponinas/química , Saponinas/aislamiento & purificación , Bazo/metabolismo , Bazo/ultraestructura , Triterpenos/química , Triterpenos/aislamiento & purificación , Viscosidad/efectos de los fármacosAsunto(s)
Cucumaria/metabolismo , Glicósidos/farmacocinética , Triterpenos/farmacocinética , Tritio , Animales , Mucosa Gástrica/metabolismo , Glicósidos/sangre , Marcaje Isotópico/métodos , Riñón/metabolismo , Hígado/metabolismo , Ratones , Ratones Endogámicos BALB C , Miocardio/metabolismo , Bazo/metabolismo , Triterpenos/sangreRESUMEN
Lipopolysaccharide-protein complex isolated from Yersinia pseudotuberculosis forms aggregates in aqueous solutions. Dissociation of aggregates was found by light scattering method for 1 M sodium chloride, 1 M guanidine chloride, and urea solutions. Very large particles were detected also in these solutions and acid media. Little light scattering alterations have been observed for 0.27 g/l solution, and pronounced effect of temperature has been detected for more diluted solutions.