RESUMEN
Ataxia-telangiectasia (AT) is a severe hereditary autosomal recessive neurodegenerative disease associated with accelerated aging and caused by mutation in both alleles of atm gene. This gene encodes a key protein of cell response to DNA damage--an ATM protein kinase. Normally, upon formation of DNA double strand breaks ATM is autophosphorylated and its active form phospho-ATM (P-ATM) appears. Here we describe a mosaic form of AT in which cells of the same patient with normal atm gene demonstrated the accumulation of P-ATM in response to DNA double-strand breaks-inducing factors whereas in cells bearing a mutant form of atm P-ATM was not detected. The epigenetic markers such as histone deacetylases SIRT1 and SIRT6, and trimethylated forms of histone H3 - H3K9me3 and H3K27me3--were studied in the nuclei of primary fibroblasts derived from patients with different forms of AT and the increase of SIRT6 level was revealed.
Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada/genética , Ataxia Telangiectasia/genética , Núcleo Celular/genética , Reparación del ADN , Fibroblastos/metabolismo , Histonas/genética , Mosaicismo , Adulto , Ataxia Telangiectasia/metabolismo , Ataxia Telangiectasia/patología , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/patología , Niño , Preescolar , Roturas del ADN de Doble Cadena , Epigénesis Genética , Femenino , Fibroblastos/patología , Histonas/metabolismo , Humanos , Lactante , Masculino , Fosforilación , Cultivo Primario de Células , Transducción de Señal , Sirtuina 1/genética , Sirtuina 1/metabolismo , Sirtuinas/genética , Sirtuinas/metabolismoRESUMEN
Ataxia-telangiectasia (AT) is a hereditary severe neurodegenerative disease developing, when mutations take place in both alleles of the atm gene, which encodes the key protein of the cellular response to DNA damage (DDR)--ATM proteinkinase. In response to the occurrence of double-strand DNA breaks, the ATM proteinkinase pass the autophosphorylation, and its active form--the phospho-ATM (P-ATM) appears in cells. In the nuclei of cells having the atm gene, P-ATM is revealed, being absent in cells with mutated forms of this gene, by means of the application of the modified method of indirect immunofluorescence. This peculiarity may be applied in the clinic, in order to confirm the diagnosis of AT.
Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada/análisis , Ataxia Telangiectasia/diagnóstico , Ataxia Telangiectasia/genética , Técnica del Anticuerpo Fluorescente Indirecta , Adolescente , Adulto , Especificidad de Anticuerpos , Ataxia Telangiectasia/patología , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Estudios de Casos y Controles , Niño , Preescolar , Roturas del ADN de Doble Cadena , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Lactante , Masculino , Mutación , Fosforilación , Cultivo Primario de CélulasRESUMEN
The qualitative differences in P53 protein stabilization after ionizing irradiation in different doses were found in cells of members of ataxia-telangiectasia (AT) family--proband AT6SP, her sister AT(S)6SP and father AT(F)6SP. The method of indirect immunofluorescence with confocal microscopy was used.
Asunto(s)
Ataxia Telangiectasia/genética , Heterocigoto , Adolescente , Adulto , Ataxia Telangiectasia/metabolismo , Células Cultivadas , Niño , Relación Dosis-Respuesta en la Radiación , Femenino , Técnica del Anticuerpo Fluorescente , Rayos gamma , Humanos , Masculino , Persona de Mediana Edad , Proteína p53 Supresora de Tumor/análisis , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/efectos de la radiaciónRESUMEN
Stabilization of P53 protein in cells isolated from patients with a grave hereditary disease ataxia-telangiectasia (AT), characterized by strongly enhanced sensitivity to ionizing radiation and impairment of cell cycle control after DNA damage, was studied. The level of expression of these reactions by patients may vary, and it tends to be linked with the severity of the disease. In all AT strains studied, both acquired by the authors and obtained from foreign colleagues, we observed the alteration of timing and character of stabilization of P53 protein, after the action of ionizing radiation in sublethal dosage, as compared to that in cells from healthy donor.
Asunto(s)
Ataxia Telangiectasia/metabolismo , Fibroblastos/efectos de la radiación , Rayos gamma , Proteína p53 Supresora de Tumor/metabolismo , Ataxia Telangiectasia/patología , Línea Celular , Niño , Preescolar , Femenino , Fibroblastos/metabolismo , Humanos , Masculino , Microscopía ConfocalRESUMEN
The paper reviews the data available in the literature on the diagnosis of brain lesions in the central form of Recklinghausen's disease (neurofibromatosis) by magnetic resonance imaging. The results of a clinical observation of 10 children suffering trom neurofibromatosis and the data of electroencephalography, computed tomography and MRI are given and analyzed. Conclusions are made on the magnitude of and the most common site of MRI changes. It is suggested that MRI shows a higher sensitivity in detecting brain lesions in Recklinghausen's disease than other diagnostic techniques.