Social isolation in rats inhibits oxidative metabolism, decreases the content of mitochondrial K-Ras and activates mitochondrial hexokinase.
Recent observations have suggested that Ras signaling includes combinations of extracellular-signal-regulated Ras activation at the plasma membrane and endomembranes, and translocation of Ras from the plasma membrane to intracellular compartments. In this study we have shown that social isolation of rat decreases the content of Bcl-2-associated K-Ras in hippocampal mitochondria, whereas the amount of H-Ras is increased in the microsomal fraction. Furthermore, we have found that galectin 1, a binding partner of activated Ras, was increased in the soluble fractions. The redistribution of Ras isoforms was accompanied by acceleration in mitochondrial hexokinase and inhibition of mitochondrial aconitase, succinate dehydrogenase, and creatine kinase, whereas the activity of aldolase, as well as cytoplasmic creatine kinase was not changed. Our data suggest that inhibition of mitochondrial oxidative metabolism by reactive oxygen species (ROS) and compensatory elevation of glycolysis in hippocampus occurs during social isolation of rats and Ras trafficking could play an important role in switching of impaired oxidative phosphorylation to anaerobic glycolysis.
Zhuravliova
Elene
E
Department of Biochemistry, I. Beritashvili Institute of Physiology, Tbilisi, Georgia.
Barbakadze
Tamar
T
Zaalishvili
Elnari
E
Chipashvili
Manana
M
Koshoridze
Nana
N
Mikeladze
David
D
D000154:Aconitate Hydratase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology / Q000378:metabolism; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism; D037483:Galectin 1 / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism*; D008124:Locomotion; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012934:Social Isolation; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
D037483:Galectin 1; D020033:Protein Isoforms; D013385:Succinate Dehydrogenase; D006593:Hexokinase; D003402:Creatine Kinase; D018631:ras Proteins; D005634:Fructose-Bisphosphate Aldolase; D000154:Aconitate Hydratase