Efeito da hiperglicemia nos canais para prótons sensíveis à voltagem: implicações para o diabetes mellitus

• Ano de defesa: 2016
• Autor(a) principal: Silva, Luisa Ribeiro [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Hiperglicemia; Prótons; Diabetes mellitus; Diabetes melitus
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=3603469; http://repositorio.unifesp.br/handle/11600/46966

Diabetes mellitus type I results from a autoimmune destruction of the pancreatic beta cells which determines the clinic condition of hyperglycemia associated with hypoinsulinemia. Advanced stages of the disease are associated with metabolic complications which result in disfunction and loss of cell mass. Several studies correlates oxidative stress with the development, and has demonstrated a relevant role for NADPH oxidase. The voltage gated proton channels (Hv1) play an important role in intracellular pH and membrane potential regulation during changes in extracellular pH in physiological and pathological situations, besides being closely related with NADPH oxidase. However, modulation of expression and/or activity of Hv1 channels and its relationship with NADPH oxidase activity in this disease is still absent in the literature. Therefore, we studied this relationship in microglia from mice embryos of diabetic mothers (DM group) or not (control group). In relation with the eletrophysiological characterization, no significant differences in the maximum aplitude of the currents between the groups were found. However, when the cells were cultived in high glucose there was a reduction of the proton current. This same effect was noted by transfecting the hHv1 fused with GFP in COS7 cells. Visualizing these cells in a confocal microscopy, we observed a diffuse localization of the channel in cells exposed to 25 mM of glucose for 24 hours, in contrast with smaller concentrations of glucose, where we clearly saw in the membrane. Considering our results, we concluded that high glucose exposure reduces the maximum proton current in microglia and heterologous system of expression, altering not only biophysical properties of the voltage gated proton channel but also its availability in the plasma membrane.