RESUMEN
Four polyhydroxylated steroids, new (20R)-5alpha-cholestan-3beta,6alpha,8,15alpha,24,26-hexaol (I) and known (20R,25S)-5alpha-cholestan-3beta6alpha,8,15beta,16beta,26-hexaol, (20R,25S)-5alpha-cholestan-3beta,6alpha,15beta,16beta,26-pentaol, and marthasterone sulfate were isolated from the Solaster endeca starfish inhabiting the Sea of Okhotsk and characterized. Steroid (I) contains a 24,26-dihydroxylated side chain, which is uncommon for starfish polyols. The isolated steroids and related metabolites from two starfish species of the Evasterias genus (in total, 15 compounds) were weakly cytotoxic in a human HeLa cell culture and some of them were inhibitors of nonspecific esterase from mouse Ehrlich carcinoma. The effects of these compounds on the p53 protein activity were studied in a yeast two-hybrid test system and both inhibitors and stimulators of this activity were found among them.
Asunto(s)
Estrellas de Mar/química , Esteroides/aislamiento & purificación , Animales , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Esterasas/antagonistas & inhibidores , Humanos , Técnicas In Vitro , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Espectroscopía de Resonancia Magnética , Ratones , Ratones Endogámicos BALB C , Estallido Respiratorio , Estereoisomerismo , Esteroides/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Técnicas del Sistema de Dos HíbridosRESUMEN
The ability of tick-borne encephalitis (TBE) virus to cause programmed cell death (apoptosis) in viral infection of newborn mice and of two cell cultures is studied. The time course of virus antigen accumulation detected by enzyme immunoassay and of endonuclease fragmentation of nuclear DNA detected by agarose gel electrophoresis is compared. All three TBE strains differing by the source of isolation and biological characteristics can cause oligonucleosomal fragmentation of DNA of brain cells of two-day white mice and of SPEV cells in acute infection. In VERO-E6 cells the same three strains caused a latent infection; accumulation of virus antigen was not associated with endonuclease fragmentation of DNA or any other signs of cytopathic destruction. These data indicate that TBE virus can cause programmed cell death both in vitro and in vivo, which is apparently one mechanism of the cytopathic effect of the virus.
Asunto(s)
Apoptosis , Efecto Citopatogénico Viral , Virus de la Encefalitis Transmitidos por Garrapatas/patogenicidad , Animales , Animales Recién Nacidos , Antígenos Virales/análisis , Línea Celular , Chlorocebus aethiops , Virus de la Encefalitis Transmitidos por Garrapatas/inmunología , Virus de la Encefalitis Transmitidos por Garrapatas/aislamiento & purificación , Ratones , Porcinos , Células Vero , Latencia del VirusRESUMEN
Molecular characteristics of 38 strains of tick-borne encephalitis (TBE) virus isolated in the Southern Sikhote-Alin focus were studied using 10 synthetic oligonucleotide probes complementary to the genomic RNA of the Sofyin strain. The isolated strains were divided into 4 groups, depending on the source of isolation: 1) strains isolated from Ixodes persulcatus (n = 8); 2) from the brain of patients dead from TBE (n = 10); 3) from the blood of patients with the febrile form of TBE (n = 7); and 4) from the blood of patients with an unapparent infection (n = 13). The total level of hybridization in the four groups was as follows: 61.8, 75.2, 55.8, and 35.2%. The "tick" strains with a great variety of the genofund are regarded as the stock group of the natural TBE virus population, 40% of which are strains close by their characteristics to avirulent strains of TBE virus.