Efeitos da restrição de ferro sobre o metabolismo da dopamina e as propriedades bioquímicas da PrPC e α­-sinucleína

• Ano de defesa: 2016
• Autor(a) principal: Pino, Jessica Monteiro Volejnik [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: Príon; Sinucleína; Dopamina; Restrição de ferro estresse oxidativo
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=3628911; http://repositorio.unifesp.br/handle/11600/48837

Deposition of protein aggregates is one of the characteristics of neurodegenerative diseases, and reactive oxygen species (ROS) seems to contribute to this phenomenon. ROS can be produced by several metabolic pathways and the dopamine metabolism is one of examples. Current evidence show that dopamine metabolites can react with cellular príon protein (PrPC) and α­-synuclein generating aggregates. Considering that the iron availability can affect dopamine metabolism, this study aimed to evaluate the effects of iron deficiency on dopamine metabolism and on the biochemical properties of PrPC and α­-synuclein. C57BL/6 mice were fed with iron restricted diet (RF) or with normal diet (CTL) for one month. Iron restriction for one month was sufficient to reduce the iron and ferritin levels in the liver of RF animals. The ferritin reduction was also observed in the hippocampus of RF group, however an increase of ferritin levels was observed in striatum of the same animals, suggesting the occurrence of redistribution of iron pool. The levels of transferrin receptors were not changed, indicating that iron deficiency was not severe. Iron restriction produced distinct effects on dopamine metabolism in the studied regions. In the striatum, dopamine levels and its metabolites DOPAC and HVA were diminished. In the pre-frontal cortex, only HVA levels were augmented along with the MAO-A activity. In the hippocampus, no alterations of dopamine metabolism have been observed. However, iron restriction increased lipid peroxidation in hipocampus. PrPC protein levels were augmented only in the striatum of RF animals, while the α­-synuclein levels did not change in any regions. Although PrPC levels were not altered in hippocampus, PrPC became less soluble after iron restriction. The alteration in dopamine metabolism induced by iron restriction does not seem to directly influence the protein levels of PrPC and α­-synuclein. On the other hand, the iron restriction itself appears to affect PrPC expression and its solubility.