Mitochondrial Oxidative Stress and Damage to Rat Brain in Copper Overload

SEMPRINE, J; MUSACCO SEBIO, R; SAPORITO, C.; ARAUJO, J; GARCÍA MAGRO, N; BOVERIS, A; REPETTO, M.

Chascomus

Congreso; IV Congreso Latinoamericano de Química Bioinorgánica (IVLABIC); 2014

It has recently increased the interest of copper (Cu) participation in the pathogenesis of neurodegenerative diseases, as acute Cu overload is associated to mitochondrial dysfunction and oxidative damage in rat brain1. The mammalian brain is a highly evolved organ with a very active aerobic metabolism. For instance, the human brain while accounting for only 2% of body weight receives 15% of the cardiac output and takes 25% of total glucose consumption and 20% of total body O2 uplake1. In addition, the brain has limited glycogen and fat reserves with a low anaerobic metabolic activity1. Thus, dyshomeostasis or situations disrupting the well coupled reactions of mitochondrial energy production have deleterious effects in the brain with eventual lethal consequences. In Cu overload, brain Cu contents were hyperbolically related to metal doses1. The mammalian brain, as a fully aerobic organ, requires Cu for essential mitochondrial energy yielding processes. Cu is in the catalytic centres of cytochrome oxidase and of Cu,Zu?SOD2. This is the major cuproenzyme of the brain and constitutes the 25% of total brain Cu2. Brain mitochondrial Cu is restricted to cytochrome oxidase and accounts for about 2 μg Cu/g wet brain in rats and humans. The brain content of cytosolic Cu,Zn-S0D accounts for 1 μg Cu/g wet brain in rats and 4 μg Cu/g wet brain in humans3. The aim of this work is to evaluate acute Cu toxicity on mitochondrial oxidative stress and damage and the association with the mitochondrial activity in rat brain, through the analysis of the time course of the phospholipids and proteins oxidation processes.