Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros








Intervalo de ano de publicação
1.
Arch. endocrinol. metab. (Online) ; 63(2): 142-147, Mar.-Apr. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1001213

RESUMO

ABSTRACT Objective: To verify the physiological action of triiodothyronine T3 on the expression of transforming growth factor α (TGFA) mRNA in MCF7 cells by inhibition of RNA Polymerase II and the MAPK/ERK pathway Materials and methods: The cell line was treated with T3 at a physiological dose (10−9M) for 10 minutes, 1 and 4 hour (h) in the presence or absence of the inhibitors, α-amanitin (RNA polymerase II inhibitor) and PD98059 (MAPK/ERK pathway inhibitor). TGFA mRNA expression was analyzed by RT-PCR. For data analysis, we used ANOVA, complemented with the Tukey test and Student t-test, with a minimum significance of 5%. Results: T3 increases the expression of TGFA mRNA in MCF7 cells in 4 h of treatment. Inhibition of RNA polymerase II modulates the effect of T3 treatment on the expression of TGFA in MCF7 cells. Activation of the MAPK/ERK pathway is not required for T3 to affect the expression of TGFA mRNA. Conclusion: Treatment with a physiological concentration of T3 after RNA polymerase II inhibition altered the expression of TGFA. Inhibition of the MAPK/ERK pathway after T3 treatment does not interfere with the TGFA gene expression in a breast adenocarcinoma cell line.


Assuntos
Humanos , Feminino , Tri-Iodotironina/genética , Neoplasias da Mama/genética , Adenocarcinoma/genética , Regulação Neoplásica da Expressão Gênica/genética , Fator de Crescimento Transformador alfa/genética , Sistema de Sinalização das MAP Quinases/genética , Tri-Iodotironina/metabolismo , Tri-Iodotironina/farmacologia , Proto-Oncogenes/genética , Neoplasias da Mama/metabolismo , RNA Mensageiro/genética , Adenocarcinoma/metabolismo , Fator de Crescimento Transformador alfa/efeitos dos fármacos , Fator de Crescimento Transformador alfa/metabolismo , Linhagem Celular Tumoral/metabolismo , Células MCF-7/metabolismo
2.
Arch Endocrinol Metab ; 63(2): 142-147, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30916164

RESUMO

OBJECTIVE: To verify the physiological action of triiodothyronine T3 on the expression of transforming growth factor α (TGFA) mRNA in MCF7 cells by inhibition of RNA Polymerase II and the MAPK/ERK pathway. MATERIALS AND METHODS: The cell line was treated with T3 at a physiological dose (10-9M) for 10 minutes, 1 and 4 hour (h) in the presence or absence of the inhibitors, α-amanitin (RNA polymerase II inhibitor) and PD98059 (MAPK/ERK pathway inhibitor). TGFA mRNA expression was analyzed by RT-PCR. For data analysis, we used ANOVA, complemented with the Tukey test and Student t-test, with a minimum significance of 5%. RESULTS: T3 increases the expression of TGFA mRNA in MCF7 cells in 4 h of treatment. Inhibition of RNA polymerase II modulates the effect of T3 treatment on the expression of TGFA in MCF7 cells. Activation of the MAPK/ERK pathway is not required for T3 to affect the expression of TGFA mRNA. CONCLUSION: Treatment with a physiological concentration of T3 after RNA polymerase II inhibition altered the expression of TGFA. Inhibition of the MAPK/ERK pathway after T3 treatment does not interfere with the TGFA gene expression in a breast adenocarcinoma cell line.


Assuntos
Adenocarcinoma/genética , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica/genética , Sistema de Sinalização das MAP Quinases/genética , Fator de Crescimento Transformador alfa/genética , Tri-Iodotironina/genética , Adenocarcinoma/metabolismo , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral/metabolismo , Feminino , Humanos , Células MCF-7/metabolismo , Proto-Oncogene Mas , Proto-Oncogenes/genética , RNA Mensageiro/genética , Fator de Crescimento Transformador alfa/efeitos dos fármacos , Fator de Crescimento Transformador alfa/metabolismo , Tri-Iodotironina/metabolismo , Tri-Iodotironina/farmacologia
3.
Physiol Rep ; 6(3)2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29388360

RESUMO

Thyroid hormones play an important role in glucose metabolism and there is evidence of increased prevalence of thyroid dysfunction in obese and diabetic patients. This study aimed at evaluating the thyroid function and the effects of the triiodothyronine (T3) treatment on glycemia control, insulin sensitivity and subclinical inflammation in cafeteria-diet-induced obesity in rats. Obesity was induced in male Wistar rats by offering a cafeteria diet and a subset of the obese rats was treated with T3 (1.5 µg per 100 g of body weight) for a 28-day period. The pituitary-thyroid axis was evaluated by molecular and biochemical parameters. Cytokine content was measured in the serum as well as in the mesenteric and epididymal white adipose tissue. Obese rats exhibited impairment of glycemia control, increased content of inflammatory cytokines in mesenteric white adipose tissue, decreased serum thyrotropin (TSH) concentration and increased sodium/iodide symporter (NIS) and TSH receptor (TSHR) protein content in thyroid gland. T3 treatment improved insulin sensitivity, glucose tolerance, and reduced inflammatory cytokine content in mesenteric white adipose tissue. In the thyroid gland NIS, TSHR, and thyroperoxidase (TPO) content were reduced while thyroglobulin (TG) content was increased by T3. The thyrotrophic response to negative feedback exerted by T3 was preserved in obese rats. The present data reinforce the beneficial effects of T3 treatment of obese rats on the improvement of insulin sensitivity and on the negative modulation of inflammatory cytokine expression in adipose tissue. Moreover, we have evidenced that the pituitary-thyroid axis is affected in obese rats, as illustrated by the impaired TSH secretion.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Citocinas/sangue , Resistência à Insulina , Obesidade/metabolismo , Tri-Iodotironina/farmacologia , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Citocinas/metabolismo , Retroalimentação Fisiológica , Masculino , Ratos , Ratos Wistar , Receptores da Tireotropina/metabolismo , Simportadores/metabolismo , Tireoglobulina/metabolismo , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Tireotropina/sangue
4.
Physiol Rep ; 4(18)2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27655796

RESUMO

The thyroid hormone (TH) plays an important role in glucose metabolism. Recently, we showed that the TH improves glycemia control by decreasing cytokines expression in the adipose tissue and skeletal muscle of alloxan-induced diabetic rats, which were also shown to present primary hypothyroidism. In this context, this study aims to investigate whether the chronic treatment of diabetic rats with T3 could affect other tissues that are involved in the control of glucose homeostasis, as the liver and kidney. Adult Male Wistar rats were divided into nondiabetic, diabetic, and diabetic treated with T3 (1.5 µg/100 g BW for 4 weeks). Diabetes was induced by alloxan monohydrate (150 mg/kg, BW, i.p.). Animals showing fasting blood glucose levels greater than 250 mg/dL were selected for the study. After treatment, we measured the blood glucose, serum T3, T4, TSH, and insulin concentration, hepatic glucose production by liver perfusion, liver PEPCK, GAPDH, and pAKT expression, as well as urine glucose concentration and renal expression of SGLT2 and GLUT2. T3 reduced blood glucose, hepatic glucose production, liver PEPCK, GAPDH, and pAKT content and the renal expression of SGLT2 and increased glycosuria. Results suggest that the decreased hepatic glucose output and increased glucose excretion induced by T3 treatment are important mechanisms that contribute to reduce serum concentration of glucose, accounting for the improvement of glucose homeostasis control in diabetic rats.

5.
Cell Biochem Biophys ; 59(2): 89-97, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20809180

RESUMO

Many macrophage functions are modulated by fatty acids (FAs), including cytokine release, such as tumor necrosis factor-α (TNF-α). TNF-α is of great interest due to its role in the inflammation process observed in several diseases such as rheumatoid arthritis, atherosclerosis, and obesity. However, the mechanisms by which FA effects occur have not been completely elucidated yet. In this study, we used a mouse monocyte lineage (J774 cells) to evaluate the effect of 50 and 100 µM of saturated (palmitic and stearic acids), monounsaturated (oleic acid) and polyunsaturated (linoleic acid) FAs on TNF-α production. Alterations in gene expression, poly(A) tail length and activation of transcription factors were evaluated. Oleic and linoleic acids, usually known as neutral or pro-inflammatory FA, inhibited LPS-induced TNF-α secretion by the cells. Saturated FAs were potent inducers of TNF-α expression and secretion under basal and inflammatory conditions (in the presence of LPS). Although the effect of the saturated FA was similar, the mechanism involved in each case seem to be distinct, as palmitic acid increased EGR-1 and CREB binding activity and stearic acid increased mRNA poly(A) tail. These results may contribute to the understanding of the molecular mechanisms by which saturated FAs modulate the inflammatory response and may lead to design of associations of dietary and pharmacological strategies to counteract the pathological effects of TNF-α.


Assuntos
Ácidos Graxos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/farmacologia , Macrófagos/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Animais , Células Cultivadas , Ácido Linoleico/farmacologia , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Ácido Oleico/farmacologia , Ácidos Esteáricos/farmacologia , Fatores de Transcrição/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética
6.
Mol Cell Endocrinol ; 240(1-2): 82-93, 2005 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-16024167

RESUMO

The GLUT4 gene transcriptional activity has a profound impact on the insulin-mediated glucose disposal and it is, therefore, important to understand the mechanisms underlying it. Insulin and exercise modulate GLUT4 expression in vivo, but the net control and involved mechanisms of each one have not been established yet. This paper sought to discriminate, in soleus muscle, the effects of insulin and muscle contraction on GLUT4 gene expression, and the involvement of transcriptional factors: myocite enhancer factor 2 (MEF2 A/C/D), hypoxia inducible factor 1-a (HIF1-a) and nuclear factor-kappa B (NF-kappaB). The GLUT4 mRNA was reduced by fasting (40%), and increased by in vitro incubation with insulin (25%) or insulin plus glucose (40%), which was accompanied by opposite regulations of NF-kappaB mRNA. Differently, in vitro, muscle contraction led to a rapid increase (35-80%) in GLUT4, MEF2A, MEF2D and HIF1-a mRNAs. Additionally, electrophoretic mobility shift assay confirmed changes in the binding activity of nuclear proteins to consensus NF-kappaB, GLUT4-Ebox and GLUT4-AT-rich element probes, parallel to the mRNA changes of their respective transcriptional factors NF-kappaB, HIF1-a and MEF2s. Concluding, insulin- and contraction-induced regulation of GLUT4 expression involves distinct transcriptional factors.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Insulina/fisiologia , Contração Muscular , Músculo Esquelético/fisiologia , Fatores de Transcrição/metabolismo , Animais , Proteínas de Ligação a DNA/genética , Jejum , Expressão Gênica/efeitos dos fármacos , Insulina/farmacologia , Fatores de Transcrição MEF2 , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Fatores de Regulação Miogênica/genética , Fatores de Regulação Miogênica/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Nucleares/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fatores de Transcrição/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA