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Cyclosporin A induces apoptosis in rat hepatocytes in culture.
Román, I D; Rodríguez-Henche, N; Fueyo, J A; Zueco, J A; Menor, C; Prieto, J C; Guijarro, L G.
Afiliación
  • Román ID; Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Alcalá de Henares, Spain.
Arch Toxicol ; 72(9): 559-65, 1998 Sep.
Article en En | MEDLINE | ID: mdl-9806427
Cyclosporin A (CsA) at concentrations up to 1 microM induced apoptosis in a dose-dependent manner in cultured rat hepatocytes for 48 h in the presence of insulin and epidermal growth factor (EGF). The effect of CsA was evidenced by the DNA fragmentation pattern constituted by fragments of multiples of 180-200 base pairs, which is a characteristic of programmed cell death. The metabolic activity did not change significantly in the presence of 0.1 microM CsA and diminished to 49% of control in the presence of 1 microM CsA. Changes in the metabolic activity were correlated with a decrease in both [methyl-3H]thymidine uptake and DNA content, which reflects a decrease in the cell number. The treatment of cells with CsA (1 microM) decreased the metabolic activity/DNA content ratio by 24% with respect to dimethyl sulphoxide (DMSO) control, which also suggests, under these conditions, that the necrosis achieved is at most only 24%. In addition, the changes observed (apoptotic process, arrest of the cell cycle and apparition of a necrotic process) were correlated with an increase in the high-affinity guanosine triphosphatase (GTPase) enzymes.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ciclosporina / Apoptosis / Hígado Límite: Animals Idioma: En Revista: Arch Toxicol Año: 1998 Tipo del documento: Article País de afiliación: España Pais de publicación: Alemania
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ciclosporina / Apoptosis / Hígado Límite: Animals Idioma: En Revista: Arch Toxicol Año: 1998 Tipo del documento: Article País de afiliación: España Pais de publicación: Alemania