Reactive oxygen species generation is modulated by mitochondrial kinases: correlation with mitochondrial antioxidant peroxidases in rat tissues.
Mitochondrial hexokinase (mt-HK) and creatine kinase (mt-CK) activities have been recently proposed to reduce the rate of mitochondrial ROS generation through an ADP re-cycling mechanism. Here, we determined the role of mt-HK and mt-CK activities in regulate mitochondrial ROS generation in rat brain, kidney, heart and liver, relating them to the levels of classical antioxidant enzymes. The activities of both kinases were significantly higher in the brain than in other tissues, whereas the activities of catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were higher in both liver and kidney mitochondria. In contrast, manganese superoxide dismutase (Mn-SOD) activity was not significantly different among these tissues. Activation of mitochondrial kinases by addition of their substrates increased the ADP re-cycling and thus the respiration by enhancing the oxidative phosphorylation. Succinate induced hydrogen peroxide (H(2)O(2)) generation was higher in brain than in kidney and heart mitochondria, and the lowest in liver mitochondria. Mitochondrial membrane potential (DeltaPsi(m)) and H(2)O(2) production, decreased with additions of 2-DOG or Cr to respiring brain and kidney mitochondria but not to liver. The inhibition of H(2)O(2) production by 2-DOG and Cr correspond to almost 100% in rat brain and about 70% in kidney mitochondria. Together our data suggest that mitochondrial kinases activities are potent preventive antioxidant mechanism in mitochondria with low peroxidase activities, complementing the classical antioxidant enzymes against oxidative stress.
Santiago
Ana Paula S A
AP
Instituto de Biofísica Carlos Chagas Filho, Programa de Biologia Celular e Parasitologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Chaves
Elen Aguiar
EA
Oliveira
Marcus F
MF
Galina
Antonio
A
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D009928:Organ Specificity; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013379:Substrate Specificity
D000975:Antioxidants; D017382:Reactive Oxygen Species; D000244:Adenosine Diphosphate; D006861:Hydrogen Peroxide; D009195:Peroxidase; D010770:Phosphotransferases; D010100:Oxygen