RESUMEN
Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs.
Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Regulación de la Expresión Génica/genética , Neuronas/metabolismo , Obesidad/fisiopatología , Proteínas Adaptadoras Transductoras de Señales/sangre , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Tejido Adiposo/metabolismo , Adulto , Anciano , Análisis de Varianza , Apolipoproteína A-I/sangre , Apolipoproteína A-I/genética , Apolipoproteína A-I/metabolismo , Proteínas Reguladoras de la Apoptosis/sangre , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ensayo de Inmunoadsorción Enzimática , Femenino , Perfilación de la Expresión Génica , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Factores de Crecimiento Nervioso/sangre , Factores de Crecimiento Nervioso/genética , Factores de Crecimiento Nervioso/metabolismo , Páncreas/metabolismo , Proteínas Proto-Oncogénicas c-vav/sangre , Proteínas Proto-Oncogénicas c-vav/genética , Proteínas Proto-Oncogénicas c-vav/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sinaptotagminas/sangre , Sinaptotagminas/genética , Sinaptotagminas/metabolismoRESUMEN
The aim of this study was to investigate the effect of magnesium oxide nanoparticles (MgO NPs) and MgO NPs coated with glucose (MONPCG) on Leishmania (L) major. First, the promastigotes of L. major were separately incubated with serial concentrations of MgO NPs and MONPCG for 24, 48, and 72 h at 37 °C. Then, the cell viability of promastigotes was evaluated by MTT assay. On the other hand, the relative expression of Cpb and GP63 genes was detected by quantitative-real time PCR. Based on results, the increase of concentration, both MgO NPs and MONPCG, and incubation time led to decrease of cell viability. Moreover, the expression of Cpb and GP63 genes was decreased with increase of concentration of MgO NPs and MONPCG. Also, the increase of incubation time led to decrease of their expression in MgO NPs treated promastogotes. But, in case of MONPCG treated promastogotes, the increase of incubation time did not change the expression of Cpb and GP63. Interestingly, MONPCG could silence Cpb and GP63 genes better than MgO NPs. Note, the capability was also seen at sub-toxic concentrations of MONPCG.