Perfil de expressão dos genes APEX1, OGG1 e PARP1 em células do sangue periférico de pessoas com a Síndrome de Berardinelli-Seip do Nordeste do Brasil

Abstract

Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare recessive autosomal disease characterized by nearly complete absence of adipose tissue, resulting in disturbs on carbohydrates and lipids metabolism, insulin resistance and variable cognitive impairments. It was described that northeastern Brazil has the higher BSCL prevalence in the country. Recently, some studies suggested a role of reactive oxygen species (ROS) on BSCL physiopathology. Moreover, mitochondrial dysfunction leading to oxidized DNA damage has been associated to the mutations found in BSCL patients. Since Base Excision DNA Repair (BER) pathway is involved in the removal of oxidized DNA lesions, the purpose of this study was to evaluate the mRNA expression profile of the mainly BER enzymes (APE-1, OGG1 and PARP-1) in BSCL peripheral blood cells and analyze the rate of oxidative damaged purines in those genomes. The results showed an increase of 305% and 335% on APEX1 and OGG1 mRNA expression mean, respectively, while an increase of 65% was observed on PARP1 mRNA expression mean in peripheral blood cells of BSCL people when compared with controls. We also observed almost equivalent averages between the rates of damage purines in the genome compared with controls. We supposed that the oxidative lesion rate between these groups is almost the same. The necessity of an enhanced transcription to supply a DNA repair demand on BSCL people could explain the equivalence between DNA oxidative damage between the groups. However, APE-1 and OGG-1 could have been recruited not only to repair, but also to another pathways in that peripheral blood cells. Besides, PARP-1 downregulation is an expected phenomenon in adipose tissue disturbance, because of relation between that enzyme functions and adipocyte differentiation.