Electron leakage from electron transport chain in mitochondria is the major source of cellular reactive oxygen species (ROS), providing a continuous generation of these toxic byproducts. It have been well established that 1-2% of the consumed O₂ by the respiratory chain is diverted to generate ROS. The rate of ROS production is dependent on mitochondrial membrane potential (DYm) and inversely proportional to the availability of ADP. Our group showed that mitochondrial ADP re-cycling kinases, hexokinase (mt-HK) and creatine kinase (mt-CK) play a role on preventing ROS generation in rat brain. In this study we investigate if there is any correlation between classical antioxidant defenses and these ADP generating kinases using three different tissues which exhibit distinct oxidative stress sensitivities such as, rat brain, kidney and liver. The antioxidant enzymes catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) were higher in kidney and in liver than in brain. Our results also shown that superoxide dismutase (SOD) activities did not vary significantly among these tissues. Curiously, rat brain mitochondria have higher levels of mitochondrial kinases than those classical antioxidant enzymes when compared with the two other tissues. In subsequent experiments it was used not only different organs, but the mitochondria were isolated from mice at different stages of earlier postnatal development. The specific activities of mt-HK and mt-CK significantly increase with aging, whereas the activities of antioxidant enzymes display an age-dependent decline.
These results indicate an inverse correlation between the levels of classical antioxidant defenses and the efficiency of the ADP-generating kinases to disturb the mitochondrial bioenergetic parameters and ROS production.
Supported by: FAPERJ, CNPq