RESUMO
The effect of inhibition of the tumor suppressor p53 on the antioxidant system genes expression under the influence of cytotoxic compounds of the platinum group was studied. It was found that the action of platinum(II) and platinum(IV) complexes induced accumulation of p53 protein with a maximum in 12 h, which was confirmed by an increase in the expression of the P21 gene, the target gene of the p53 protein. It was shown that the action of platinum complexes activated the expression of catalase and superoxide dismutase 2 genes. Suppression of p53 protein functions with specific inhibitor α-piphitrin under the action of platinum complexes reduced the expression of catalase and superoxide dismutase 2 genes and the target gene P21, which attested to the p53-dependent regulation of these genes.
Assuntos
Antineoplásicos/farmacologia , Antioxidantes/metabolismo , Proteína Supressora de Tumor p53/fisiologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Catalase/efeitos dos fármacos , Catalase/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Enzimas Reparadoras do DNA/genética , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Exogenous NO donor 3,3-bis-(nitroxymethyl)oxetane (NMO) was synthesized at the Institute for Problems of Chemical Physics (Russian Academy of Sciences). This compound was shown to inhibit cell death (apoptosis and necrosis) in cyclophosphamide-sensitive and cyclophosphamide-resistant P388 murine tumor. p53 protein was expressed in both lines of tumor cells. NO donor NMO had little effect on p53 protein expression in cells of both stains. Our results suggest that the proapoptotic effect of NMO is mediated by the p53-independent molecular mechanisms.
Assuntos
Apoptose/efeitos dos fármacos , Éteres Cíclicos/farmacologia , Leucemia P388/tratamento farmacológico , Doadores de Óxido Nítrico/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Antineoplásicos Alquilantes/farmacologia , Apoptose/fisiologia , Contagem de Células , Linhagem Celular Tumoral , Ciclofosfamida/farmacologia , Resistencia a Medicamentos Antineoplásicos , Leucemia P388/patologia , Leucemia P388/fisiopatologia , Camundongos , Necrose/tratamento farmacológico , Necrose/fisiopatologia , Fatores de TempoRESUMO
We analyzed the content of lamin B, one of the main proteins of the nuclear membrane, in different chromatin fractions obtained during purification of the nuclear matrix from different cell types. Depending on cell type and nuclear matrix preparation technique, lamin B was found in different not associated with matrix chromatin compartments. This effect was observed after chromatin extraction with ammonium chloride after nucleolysis and after chromatin extraction with sodium chloride before nuclease treatment. These findings suggest that the structure of the nuclear matrix is destabilized in certain extraction procedures and that studies of subcompartmentalization of nuclear macromolecules require additional control of nuclear matrix integrity.