ABSTRACT
The antioxidant effect of succinate and 3-hydroxybutyrate oxidation on the kinetics of lipid peroxidation induced by ATP-Fe2+ complex in isolated rat liver mitochondria of old (1.0-1.5 years) and young (3 months) male rats was investigated. The rate of induced lipid peroxidation V(LPO) in rat liver mitochondria and the half-time of oxygen consumption Δt50, which included the lag period and the initiation. phase, was recorded polarographically. Without exogenous oxidative-substrates V(LPO) was slightly higher in mitochondria of old animals, but the onset of lipid peroxidation cascade was significantly earlier than in young animals. Incubation of mitochondria with 5mM succinate for 1 min inhibited V(LPO) by 15% in young animals and by 35% in old animals. However, only in mitochondria of old animals Δt50 increased by 19% as compared to lipid peroxidation without substrates. V(LPO) in mitochondria of young animals did not significantly change during 3-hydroxybutyrate oxidation, while in mitochondria of old animals it was reduced by 19% with a slight increase in Δt50. To simulate age-dependent dysfunction we damaged isolated mitochondria by a series of freeze-thaw cycles, which caused a significant increase of V(LPO) of.both age groups. Succinate oxidation inhibited V(LPO) in damaged mitochondria in all cases by 56%, as compared to V(LPO) without oxidative substrates and extended At50 twofold in mitochondria of young animals. Oxidation of 3-hydroxybutyrate had no effect on V(LPO) in damaged mitochondria regardless of animal, age and extended Δt50 by 48% in mitochondria of young animals. Thus, the antioxidant effect of succinate oxidation can prevent lipid peroxidation damage and may exhibit geroprotective action at the level of aging mitochondria. Therefore, the antioxidant effect is due to the process of substrate oxidation in the respiratory chain but not because of an interaction of their structures with membrane lipids per se.
Subject(s)
Aging/metabolism , Antioxidants/pharmacology , Mitochondria, Liver/drug effects , Succinic Acid/pharmacology , 3-Hydroxybutyric Acid/pharmacology , Adenosine Triphosphate/chemistry , Adenosine Triphosphate/pharmacology , Animals , Antioxidants/metabolism , Cations, Divalent , Culture Techniques , Electron Transport/drug effects , Iron/chemistry , Iron/pharmacology , Lipid Peroxidation/drug effects , Male , Mitochondria, Liver/metabolism , Oxygen Consumption/drug effects , Polarography , Rats , Rats, Sprague-Dawley , Succinic Acid/metabolismABSTRACT
It is known that the long-duration decline of high-energy phosphates(HP) level in skeletal muscles, induced by administration of beta-guanidinpropionic acid (beta-GPA), is followed by the increase of mitochondrial enzyme activities (MEA). The same increase of MEA was observed in the course of physical exercise training. The decrease of MEA and at the same time the increase of HP levels were found under gravitational unloading. If changes in HP level are believed to trigger on the alterations in MEA, the increase of HP levels in muscles should lead to decline of MEA as well. The present work was purposed to reveal if the changes in HP level under different contractile activity levels are associated with the changes of oxidative potential in the skeletal muscles.
Subject(s)
Guanidines/pharmacology , Hindlimb Suspension , Mitochondria, Muscle/enzymology , Muscle, Skeletal/metabolism , Oxygen Consumption/physiology , Phosphocreatine/drug effects , Propionates/pharmacology , Animals , Cell Respiration/physiology , Creatine/pharmacology , Creatine Kinase/metabolism , Male , Mitochondria, Muscle/drug effects , Mitochondria, Muscle/physiology , Muscle, Skeletal/drug effects , Muscle, Skeletal/enzymology , Muscle, Skeletal/physiology , Oxygen Consumption/drug effects , Phosphocreatine/metabolism , Rats , Rats, WistarABSTRACT
1. The causes of the suppression of oxidative phosphorylation and energy-dependent cationic transport into liver mitochondria of hibernating gophers have been analysed. 2. The decrease of the ATP synthesis rate and suppression of the energy-dependent K(+)- and Ca(2+)-transport into mitochondria during hibernation has been found to be mainly related to a delta psi decrease in mitochondria of hibernating gophers. 3. The increase delta psi upon incubation of the mitochondria of hibernating animals in a hypotonic medium results in an essential acceleration of ATP synthesis and energy-dependent cationic transport.
Subject(s)
Hibernation/physiology , Mitochondria, Liver/metabolism , Sciuridae/metabolism , Adenosine Triphosphate/biosynthesis , Animals , Calcium/metabolism , Energy Metabolism , Ion Transport , Oxidative Phosphorylation , Potassium/metabolismABSTRACT
1. In the present work the initially lowered oxidase activity of liver mitochondria of hibernating gophers is shown to increase upon Ca(2+)-loading, after freezing-thawing repeated three times and after swelling in a medium containing potassium acetate as well as in a hypotonic sucrose medium. 2. In all cases the inhibition of phospholipase A2 hindered the increase of the oxidase activity of mitochondria. 3. Mitochondria of hibernating gophers have a lowered delta psi in comparison with active animals, which is restored in the hypotonic medium.
Subject(s)
Hibernation/physiology , Mitochondria, Liver/metabolism , Phospholipases A/metabolism , Sciuridae/metabolism , Animals , In Vitro Techniques , Intracellular Membranes/metabolism , Membrane Potentials , Oxidoreductases/metabolism , Oxygen Consumption , Phospholipases A2ABSTRACT
1. The rates of oxidation of various substrates (beta-hydroxybutyrate, succinate, ascorbate + TMPD) and the rate of ATP synthesis in liver mitochondria from active and hibernating ground squirrels were measured. 2. It was shown that the rate of mitochondrial respiration is significantly lower in hibernating animals than in active animals. 3. The degree of inhibition of mitochondrial respiration in hibernating ground squirrels was found to correlate with the length of the respiratory chain fragment involved in the oxidation of a given substrate. 4. The inhibition of mitochondrial respiration in hibernating animals was accompanied by a decrease in the rate of ATP synthesis. 5. The activity of phospholipase A2 in liver mitochondria from hibernating ground squirrels was found to be decreased. The activation of phospholipase A2 by Ca2+ ions eliminated the inhibition of respiration almost completely. 6. It was assumed that the inhibition of mitochondrial respiration during hibernation is (a) related to the suppression of phospholipase A2 activity and (b) caused by the reduced rates of electron transport through the respiratory chain and/or of substrate transport across the mitochondrial membrane.
