RESUMEN
OBJECTIVE: The aim of the present study was to examine the effect of chromium disilicide and titanium nitride nanoparticles on the expression level of genes encoding important regulatory factors (IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK/NUAK2, CD36, and PECAM1/CD31) in mouse liver for evaluation of possible toxic effects of these nanoparticles. METHODS: Male mice received 20 mg chromium disilicide nanoparticles (45 nm) and titanium nitride nanoparticles (20 nm) with food every working day for 2 months. The expression of IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver was studied by quantitative polymerase chain reaction. RESULTS: Treatment of mice with chromium disilicide nanoparticles led to down-regulation of the expression of IGFBP2, IGFBP5, PECAM1, and SNARK genes in the liver in comparison with control mice, with more prominent changes for SNARK gene. At the same time, the expression of IGFBP3 and CD36 genes was increased in mouse liver upon treatment with chromium disilicide nanoparticles. We have also shown that treatment with titanium nitride nanoparticles resulted in down-regulation of the expression of IGFBP2 and SNARK genes in the liver with more prominent changes for SNARK gene. At the same time, the expression of IGFBP3, IGFBP4, and CD36 genes was increased in the liver of mice treated with titanium nitride nanoparticles. Furthermore, the effect of chromium disilicide nanoparticles on IGFBP2 and CD36 genes expression was significantly stronger as compared to titanium nitride nanoparticles. CONCLUSIONS: The results of this study demonstrate that chromium disilicide and titanium nitride nanoparticles have variable effects on the expression of IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver, which may reflect the genotoxic activities of the studied nanoparticles.
Asunto(s)
Expresión Génica/efectos de los fármacos , Hígado/efectos de los fármacos , Nanopartículas , ARN Mensajero/efectos de los fármacos , Titanio/farmacología , Animales , Antígenos CD36/efectos de los fármacos , Antígenos CD36/genética , Compuestos de Cromo/farmacología , Regulación hacia Abajo , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/efectos de los fármacos , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/efectos de los fármacos , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/efectos de los fármacos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 4 de Unión a Factor de Crecimiento Similar a la Insulina/efectos de los fármacos , Proteína 4 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Hígado/metabolismo , Masculino , Ratones , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/efectos de los fármacos , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , Reacción en Cadena de la Polimerasa , Proteínas Serina-Treonina Quinasas/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Compuestos de Silicona/farmacología , Regulación hacia ArribaRESUMEN
Identify and prevent possible adverse effects of nanostructures under conditions of industrial production is the primary hygienic problem is not resolved at this time. In order to approach to solve a series of physiological, hygienic and toxicological studies. Study of harmful production factors in different technologies of metal nanoparticles, analyzed the health of workers employed in manufacturing them. Also established specific mechanisms of toxicity of nanosilver nanometals for example, the technique of hygienic control over the content in the air of the working area metal nanoparticles, the data on the existing approaches to the hygienic standardization of nanoscale objects in the breathing zone of workers.
Asunto(s)
Compuestos de Bario/toxicidad , Expresión Génica/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Nanotecnología , Seguridad , Plata/toxicidad , Titanio/toxicidad , Aerosoles , Animales , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Humanos , Riñón/efectos de los fármacos , Riñón/enzimología , Pulmón/efectos de los fármacos , Pulmón/enzimología , Masculino , Persona de Mediana Edad , Miocardio/enzimología , Salud Laboral , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Ratas , Ratas Wistar , Testículo/efectos de los fármacos , Testículo/enzimología , UcraniaRESUMEN
The main goal of this work was investigation of the effect of methyl tertbutyl ether, ecologically dangerous chemical compound, on the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB-3) and vascular endothelial growth factor (VEGF) mRNA in different rat organs. Expression of PFKFB-3 and VEGF is a hypoxia inducible factor (HIF)-dependent process which significantly increases under hypoxia, in malignant tumors and other pathology. In this study we have shown that PFKFB-3 and VEGF mRNA expression in the liver, lung, and heart changes in rats, treated with methyl tertbutyl ether for two months, in organ-specific manner. Expression of alternative splice variants of PFKFB-3 mRNA as well as VEGF mRNA also changes in organ-specific manner in rats, treated with methyl tertbutyl ether. The effect of methyl tertbutyl ether on the expression of PFKFB-3 and VEGF mRNA and its alternative splice variants is dose-dependent. Results of this investigation clearly demonstrated that methyl tertbutyl ether affects the expression of PFKFB-3, a key regulatory enzyme of glycolysis, as well as VEGF, very important factor of angiogenesis, in an organ-specific and dose-dependent manner.
Asunto(s)
Contaminantes Ambientales/toxicidad , Corazón/efectos de los fármacos , Hígado/efectos de los fármacos , Pulmón/efectos de los fármacos , Éteres Metílicos/toxicidad , Fosfofructoquinasa-2/biosíntesis , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Empalme Alternativo , Animales , Relación Dosis-Respuesta a Droga , Hígado/enzimología , Hígado/metabolismo , Pulmón/enzimología , Pulmón/metabolismo , Masculino , Miocardio/enzimología , Miocardio/metabolismo , Especificidad de Órganos , Fosfofructoquinasa-2/genética , Reacción en Cadena de la Polimerasa , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Ratas , Ratas Wistar , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
Expression of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase-4 (PFKFB-4) mRNA was studied in different rat organs. Several new unique alternative splice variants of PFKFB-4 mRNA were identified. They have deletions or inserts in fructose-2,6-bisphosphatase region as well as different length and amino acid sequence of C-terminal part. However, 6-phosphofructo-2-kinase catalytic domains were identical in all variants. Moreover, the expression of different alternative splice variants of PFKFB-4 mRNA has shown tissue specificity. Expression of both alternative splice variants of PFKFB-4 mRNA significantly changed in rats treated by methyl tretbutyl ether, ecologically dangerous chemical compound. Results of this investigation indicate a possible role of PFKFB-4 splice isoforms in cell-specific regulation of glycolysis and demonstrate the sensitivity of the regulation of alternative splicing to the action of toxic chemical compounds, in particular methyl tertbutyl ether.
