RESUMO
Oxidative phosphorylation disorders are often associated with increased oxidative stress and antioxidant therapy is frequently given as treatment. However, the role of oxidative stress in oxidative phosphorylation disorders or patients is far from clear and consequently the preventive or therapeutic effect of antioxidants is highly anecdotic. Therefore, we performed a systematic study of a panel of oxidative stress parameters (reactive oxygen species levels, damage and defense) in fibroblasts of twelve well-characterized oxidative phosphorylation patients with a defect in the POLG1 gene, in the mitochondrial DNA-encoded tRNA-Leu gene (m.3243A>G or m.3302A>G) and in one of the mitochondrial DNA-encoded NADH dehydrogenase complex I (CI) subunits. All except two cell lines (one POLG1 and one tRNA-Leu) showed increased reactive oxygen species levels compared with controls, but only four (two CI and two tRNA-Leu) cell lines provided evidence for increased oxidative protein damage. The absence of a correlation between reactive oxygen species levels and oxidative protein damage implies differences in damage prevention or correction. This was investigated by gene expression studies, which showed adaptive and compensating changes involving antioxidants and the unfolded protein response, especially in the POLG1 group. This study indicated that patients display individual responses and that detailed analysis of fibroblasts enables the identification of patients that potentially benefit from antioxidant therapy. Furthermore, the fibroblast model can also be used to search for and test novel, more specific antioxidants or explore ways to stimulate compensatory mechanisms.
Assuntos
Antioxidantes/uso terapêutico , Fibroblastos/metabolismo , Doenças Mitocondriais/tratamento farmacológico , Fosforilação Oxidativa , Estresse Oxidativo , Adolescente , Adulto , Linhagem Celular , Criança , Pré-Escolar , DNA Polimerase gama , DNA Mitocondrial/genética , DNA Polimerase Dirigida por DNA/genética , Feminino , Humanos , Lactente , Masculino , Doenças Mitocondriais/metabolismo , Mutação , RNA de Transferência de Leucina/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
Nodulation factors (NFs) are lipochito-oligosaccharide signal molecules excreted by soil-living rhizobia. These molecules elicit a range of responses in the legume roots, with which the bacteria can live in symbiosis. In this review we focus on the genetic, pharmacological and cell biological approaches that have been, and are being, undertaken to decipher the signalling pathways that lead to the symbiotic responses in the plant.
