RESUMO
We investigated the toxicity of bisphenol A (BPA) by determining the gene expression of nerve growth factor (Ngf in the embryonic mouse cell line mHypoE-N44 derived from the hypothalamus exposed to BPA dose range between 0.02 and 200 µmol L-1 for 3 h. Ngf mRNA levels decreased in a dose-dependent manner, with significant reductions observed in the 2 to 50 µmol L-1 BPA treatment groups compared to controls. However, at 100 to 200 µmol L-1 the NgfmRNA gradually increased and was significantly higher than control, while the expression of the apoptosis-related genes Caspase 3 and transformation-related protein 73 decreased significantly. These results suggest that in an embryonic hypothalamic cell line the higher doses of BPA induce a unique pattern of Ngf gene expression and that BPA has the potential to suppress apoptosis essential for early-stage brain development.
Assuntos
Apoptose/efeitos dos fármacos , Apoptose/genética , Compostos Benzidrílicos/toxicidade , Expressão Gênica/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Fator de Crescimento Neural/efeitos dos fármacos , Fator de Crescimento Neural/genética , Fenóis/toxicidade , Animais , Linhagem Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hipotálamo/crescimento & desenvolvimento , Camundongos , RNA Mensageiro/efeitos dos fármacosRESUMO
DNA methyltransferases (DNMTs) are associated with epigenetic regulation of gene expression, and methyl-CpG binding protein 2 (MECP2) acts as a long-range regulator of methylated genes. We evaluated the effects of bisphenol A (BPA) on embryonic mouse hypothalamic cells, with particular emphasis on the gene expression of Dnmts (Dnmt1, Dnmt3a, and Dnmt3b) and Mecp2 isoforms. In a dose-dependent (0.02-200 µM BPA) 3-hr experiment, real-time reverse transcription polymerase chain reaction revealed that gene expression of both Dnmts and Mecp2_e2 was affected at 200 µM and that of Mecp2_e1 was affected at > 20 µM. These results suggest that gene expression of Dnmts and Mecp2 are less susceptible to lower doses of BPA in developing hypothalamic cells. However, as BPA concentration increases, this agent has the potential to alter gene expression of key players that provide stability and flexibility of epigenetic gene regulation, which could disrupt the normal development of hypothalamic functions.