Detalhes bibliográficos
Ano de defesa: |
2014 |
Autor(a) principal: |
Dias, Henrique Bregolin
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Orientador(a): |
Oliveira, Jarbas Rodrigues de
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Banca de defesa: |
Não Informado pela instituição |
Tipo de documento: |
Dissertação
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Tipo de acesso: |
Acesso aberto |
Idioma: |
por |
Instituição de defesa: |
Pontifícia Universidade Católica do Rio Grande do Sul
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Programa de Pós-Graduação: |
Programa de Pós-Graduação em Biologia Celular e Molecular
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Departamento: |
Faculdade de Biociências
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País: |
BR
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Palavras-chave em Português: |
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Área do conhecimento CNPq: |
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Link de acesso: |
http://tede2.pucrs.br/tede2/handle/tede/5503
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Resumo: |
Hereditary hemochromatosis (HH) is a genetic disease where iron balance is deregulated and this metal accumulates in the liver, causing toxic effects and fibrosis. Fibrosis is an exacerbated wound-healing response with extracellular matrix (ECM) deposition. Hepatic stellate cells (HSC), when activated, are the main responsible for ECM production. Fructose-1,6-bisphosphate (FBP) is a sugar and possess innumerous beneficial effects, like enhance cell antioxidant potential, protects liver from damage and reverts the phenotype of activated HSC. Because of this, we aimed to test the effects of FBP in immortalized HSC line (GRX) exposed to free iron (Fe) tempting to simulate what occurs in patients with HH.Fe (1mg/L) treatment for 8 days increased cell growth, whereas Fe + FBP (1mg/L + 0.6mM) decreased cell proliferation to levels below of control. LDH activity, apoptosis rate and cell cycle were not altered in any group. Oil Red-O (ORO) staining showed a decrease in lipid content when GRX cells were Fe-treated (1mg/L) for 8 days. In Fe + FBP (1mg/L + 0.6mM), GRX cells showed increased lipid content and characteristics of quiescent HSC. PPAR-γ expression was diminished on Fe group and same as control on Fe + FBP group. On the contrary, Fe treatment rose Col-1 expression and Fe + FBP reversed it to control levels. TGF-β1 was unaltered in Fe group. However, on Fe + FBP group, TGF-β1 levelswas far bellow of control and Fe-treated group, showing an antifibrotic activity. FBP didn t present antioxidant activity by DPPH assay. Ferrozine assay showed a decreased absorbance after 120 min in all FBP-tested doses, demonstrating that FBP is an iron chelator. These data demonstrate that FBP reverse the phenotype of GRX cells even when in Fepresence and that this could be caused by regulation of PPAR-γ and COL-1. In conclusion, FBP diminished the growth rate and reversed the phenotype of GRX cell, showing a possible antifibrotic effect. |