RESUMO
We compared the efficiency of delivery of plasmid DNA (active ingredient concentration 1 mg/kg) that provides production of nerve growth factor (NGF) after intravenous administration to rats and after administration by hydroporation. The method of hydroporation ensured plasmid penetration into the liver tissue and lengthened the time of its detection in the organ. DNA concentration in 1 h after its introduction by hydroporation or intravenous route was 0.7 and 0.05 ng/mg tissue, respectively. The use of this transfection method ensured preservation of NGF DNA in the liver tissue at a level of 0.24 ng/mg of tissue 1 day after administration of the plasmid construct, while after intravenous administration, expression of the analyzed DNA was not detected in blood and liver samples. After hydroporation, the maximum of relative normalized expression of cDNA (270 rel. units) was observed after 4 h, and after 1 day, this parameter decreased to 35 rel. units. Introduction of plasmid DNA of NGF by hydroporation prevented the development of disorders of neuromuscular conduction in a rats model of toxic neuropathy induced by subacute administration of malathion in a dose of 0.5 LD50.
Assuntos
Fator de Crescimento Neural/genética , Fármacos Neuroprotetores/metabolismo , Doenças do Sistema Nervoso Periférico/terapia , Plasmídeos/metabolismo , Transfecção/métodos , Animais , Citomegalovirus/genética , Citomegalovirus/metabolismo , Eletromiografia , Expressão Gênica , Injeções Intravenosas , Inseticidas/administração & dosagem , Fígado/metabolismo , Fígado/patologia , Malation/administração & dosagem , Masculino , Fator de Crescimento Neural/metabolismo , Condução Nervosa/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/patologia , Plasmídeos/química , Regiões Promotoras Genéticas , RatosRESUMO
Site-specific transcription factors of the nuclear factor 1 (NF1) family are ubiquitous, are encoded by four genes in mammals, and play a role in regulating transcription of approximately 100 cell and viral genes. The NF1 proteins are characterized by the ability to act as both transcription factors and viral replication factors and by a low affinity for nucleosomal DNA. The review considers the dual role of the NF1 family factors in hormone-mediated transactivation of mouse mammary tumor virus (MMTV) promoter: the factors are essential for both transcription activation and nucleosome remodeling. Emphasis is placed on the role of the NF1 family factors in the formation and maintenance of a preset chromatin structure in the MMTV promoter region and the regulatory elements of the lysozyme gene during macrophage differentiation. Since disruption of individual NF1 family genes caused pathological changes in human and animal tissues, the NF1 family proteins are subjects of basic and applied research.
