Decreased protein expression and trafficking underlies impaired mitochondrial DNA repair pathway in the hippocampus of ovarian hormone-deprived rats

AVACA, MICAELA; GREDILLA RICARDO; VILLA IVANA; REINÉS ANALÍA; STEVNSNER TINNA; ZÁRATE SANDRA

Congreso; Reunión Anual de Sociedades de Biociencias; 2022

Mitochondria dysfunction and oxidative stress critically affect the brain due to its high demand of energy and low antioxidant capacity. Oxidative damage to mitochondrial DNA is repaired by Base Excision Repair (BER) pathway through several steps comprising lesion-specific glycosylases and endonucleases. Ovarian hormone loss is related to brain mitochondrial dysfunction and oxidative stress. The aim of this work was to assess if hormone deprivation affects protein expression and/or mitochondrial localization of BER enzymes to explain previous results regarding differential activity of such enzymes in the hippocampus (Hp) and cerebral cortex (Cc). To this aim, adult rats were ovariectomized (OVX) or sham-operated (SHAM). After 12 weeks, we obtained cytosolic, mitochondrial and nuclear proteins from total tissue homogenates from the Hp. They were analysed by WB using antibodies for BER glycosylases NEIL1 and 2, which remove oxidized bases, and AP endonuclease1 (APE1).Both total and mitochondrial NEIL2 was lower in the Hp of OVX rats (p