A comparative study on some mitochondrial enzymes from rat brain.
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Animals↗
Biomedical subjects
R F Villa
Publications and source records attributed to R F Villa.
Adenyl cyclase system and cerebral energy state.
The energy charge potential of the cerebral adenylate system, the cerebral lactate: pyruvate system, and the cerebral glycogen level were used to characterize the cerebral energy state of the brain. Cerebral adenyl cyclase activity and cyclic AMP concentrations were investigated to evaluate their possible influence on the regulatory processes in brain metabolism. These biochemical parameters were evaluated on the cortical motor area of the brain of the beagle dog in hypovolaemic hypotension during acute hypoxia (obtained by altering the composition of the inhalation mixture) and during the post-hypoxic recovery (three minutes after the restoration of normal ventilation). This experimental model of acute hypoxia was also used for investigating the action of some substances acting at beta-adrenergic receptor level or at vascular level. The substances were perfused into the carotid artery at the rate of 0.5 ml/min for three to six minutes. During the first stage of hypoxia, the adenyl cyclase system is probably an important biochemical regulatory factor. This system becomes less important when a critical threshold is crossed (oxygen arterial partial pressure less than 25-20 mmHg) below which other factors become rate-limiting. A beta-receptor stimulating agent enhanced the mechanisms of physiological post-hypoxic recovery; inhibition of this action was obtained with a beta-receptor blocking agent. Under these experimental conditions, no correlation existed between the vascular effects of the agents and brain metabolism.
Adenosine Diphosphate↗
Drugs and brain mitochondrial enzymatic activities during post-natal development in rat.
The enzymatic activities of two mitochondrial enzymes, i.e. succinate dehydrogenase and NADH-cytochrome c reductase were investigated in the brain of rats at different stages of post-natal development. In addition, the effect of the pharmacological treatment with two drugs, nicergoline and bamethan, able to interact with the alpha or the beta receptors respectively, was evaluated. The results show that both the enzymatic activities rapidly increase in the first days of extra-uterine life, thus indicating an adaptation of mitochondrial oxidative processes to post-natal environmental conditions. The pharmacological treatment with the two drugs does not induce any changes in the enzymatic activities tested.
Animals↗
Drugs and muscular pathways of pyruvate metabolism adapted to endurance training.
Limited experimental data are so far available on drug interference at muscular level on the pathways of pyruvate metabolism activated by training. In this study, the effect of chronic treatment with caffeine and papaverine on the activity of the muscular malic enzyme, lactate dehydrogenase and glutamate-pyruvate transaminase was evaluated in the trained rat. In trained animals these drugs did not induce any significant change in the enzymatic activities studied as a whole, and particularly in glutamate-pyruvate transaminase related to an important alternative pathway of pyruvate metabolism.
Adaptation, Physiological↗
Effect of hypoxia on the cerebral energy state.
The effect of hypoxia on glycogen content, adenyl cyclase activity, cyclic 3',5'-AMP concentration, lactate: pyruvate ratio and the energy charge potential connected with the pool of adenylates was evaluated in the motor area of the cortex of beagle dogs. At first, controlled hypoxia induces activation of the adenyl cyclase system while subsequently, with PaO2 values lower than 20 mm Hg, a depression of the system is observed simultaneously with a drop of the energy charge potential. When normal oxygenation is resumed, the biochemical parameters examined tend to go back to normal even though it is still necessary to resort to anaerobic mechanisms. The intracarotid perfusion with nicergoline enhances the post-hypoxic recovery of adenyl cyclase activity, even though the ergoline derivative is inactive during the stages of hypoxic suffering of the brain studied in the present work.
Adenylyl Cyclases↗
Action of some antispasmodics on gastrointestinal muscle.
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Acetylcholine↗
Action of some drugs on performance time in mice.
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Animals↗
Modifications in cerebral lipid metabolism by severe glucose deprivation during aging.
Severe glucose deprivation causes extensive derangement of phospholipids, fatty acids and free fatty acids in cerebral cortex of rats of different ages. The hypoglycemia-induced cerebral loss of phospholipids and fatty acids persists after 60 min recovery. Changes in individual classes of lipids are largely affected by aging. In fact, during glucose deprivation and recovery, in adult animals no preferential loss of polyunsaturated fatty acids and ethanolamine phosphoglycerides occurs, suggesting that the loss could be related to oxidative rather than to peroxidative degradation. On the contrary, in senescent rats the quoted events occur, suggesting the hypothesis of a possible peroxidation of cerebral lipids. Pretreatment with some agents is performed to elucidate the aging mode of action. Papaverine (acting on macrocirculation) is uneffective, while raubasine (acting on microcirculation and metabolism) and almitrine (acting on oxygen availability) interfere with the phospholipid and fatty acid metabolism, their action being different according to the rat age.
Aging↗
Influence of aging on the acute depletion of reduced glutathione induced by electrophilic agents.
A severe age-dependent depletion of reduced glutathione (GSH) occurs in rat forebrain at 1-3 h from intraperitoneal injection of the electrophilic agents cyclohexene-1-one and cycloheptene-1-one. Chronic pretreatment with central dopamine agonists (i.e., ergot alkaloids; particularly, dihydroergocriptine) partially counteracts the GSH depletion induced in 15-month-old forebrains by the prooxidants tested. In contrast, chronic pretreatment with a vasodilator agent (i.e., papaverine) magnifies the GSH depletion.
Aging↗
The mitochondrial electron transfer alteration as a factor involved in the brain aging.
The tissutal concentrations of reduced glutathione (GSH) and the contents of some key components in the electron transfer chain (namely ubiquinone, cytochromes b, c1, c, and aa3) of the intraterminal mitochondria are measured in the forebrains from 20-, 60-, or 100-week-old Wistar rats. Moreover, in 60-week-old rats, the biochemical analyses are performed also 18 h after the induction of a peroxidative stress by cyclohexene-1-one. The rats have been i.p. pretreated for 8 weeks (7 days/week) with agents acting on macrocirculation (papaverine), carbohydrate metabolism (hopanthenate), lipid metabolism (phosphatidylcholine), energy transduction (theniloxazine), and dopaminergic system (dihydroergocriptine). Brain aging is characterized by the decrease in both GSH and mitochondrial cytochrome aa3, without changes in ubiquinone and cytochrome b populations. In the same way, the peroxidative stress induced by cyclohexene-1-one causes both a GSH depletion and an imbalance among the concentrations of the mitochondrial electron transfer carriers. Only cytochrome aa3 retains all the partially-reduced oxygen intermediates tightly bound to its active sites. Therefore, it is possible to hypothesize that an electron leakage at the level of the auto-oxidizing chain components (i.e., cytochrome b and ubiquinone populations) increases the release of activated oxygen species (superoxide radical, hydroxyl radical). The treatment with the quoted pharmacological tools suggests that GSH and mitochondrial electron transfer carriers are functionally linked, but not interdependent one another.
Aging↗
Age-related changes by hypoxia and TRH analogue on synaptic ATPase activities.
Some synaptosomal energy-requiring ATPases were evaluated in the cerebral cortex from 3- and 24-month-old normoxic rats and rats submitted to either mild or severe chronic (4 weeks) intermittent normobaric hypoxia. Furthermore, 4-week treatment with saline or TRH analogue posatireline was performed. The activities of Na+,K(+)-ATPase, low- and high-affinity Ca(2+)-ATPase, and Ca2+,Mg(2+)-ATPase were assayed in synaptosomes and synaptosomal subfractions, namely synaptosomal plasma membranes and synaptic vesicles. With the exception of the high-affinity Ca(2+)-ATPase, aging induced a decrease in the ATPase activities from normoxic rats. The adaptation to chronic intermittent mild hypoxia was characterized by an increase in the activity of Mg(2+)-ATPase in 3-month-old rats, concomitant with a decrease in the activities of: a) Na+,K(+)-ATPase and high-affinity Ca(2+)-ATPase in both 3- and 24-month-old rats, and b) Ca2+,Mg(2+)-ATPase in 3-month-old ones. The TRH analogue posatireline increased the high-affinity Ca(2+)-ATPase in both 3- and 24-month-old hypoxic rats, concomitant with an increase in Mg(2+)-ATPase activity in 24-month-old ones. The adaptation to chronic intermittent severe hypoxia was characterized by a decrease in the activities of: a) Na+,K(+)-ATPase, Ca2+,Mg(2+)-ATPase and high-affinity Ca(2+)-ATPase in both 3- and 24-month-old rats, and b) low-affinity Ca(2+)-ATPase only in 24-month-old ones. The effect on Mg(2+)-ATPase activity was characterized by a decrease in the enzymatic form located in the synaptic plasma membranes, concomitant with an increase in the form located in the synaptic vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Triphosphatases↗
Age-related alterations of skeletal muscle metabolism by intermittent hypoxia and TRH-analogue treatment.
The characteristics of the energy metabolism were evaluated in the gastrocnemius muscle from 3- and 24-month-old rats in normoxia or subjected to either mild or severe chronic (4 weeks) intermittent normobaric hypoxia. Furthermore, 4-week treatment with saline or the TRH-analogue posatireline was performed. The muscular concentration of the following metabolites related to the energy metabolism was evaluated: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, lactate-to-pyruvate ratio; citrate, alpha-ketoglutarate, succinate, malate; aspartate, glutamate, alanine; ammonia; ATP, ADP, AMP, creatine phosphate; energy charge potential. Furthermore the maximum rate of the following muscular enzymes was evaluated: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; citrate synthase, malate dehydrogenase; total NADH cytochrome c reductase; cytochrome oxidase. The age-related decrease in muscular glucose 6-phosphate, pyruvate and alanine concentrations and increase in citrate concentration were consistent with the age-related decreased hexokinase and increased citrate synthase activities. Ageing was characterized by a decrease in muscular creatine phosphate concentration, while the energy mediators and the energy charge potential were unchanged. The chronic (4 weeks) intermittent normobaric mild and severe hypoxia-induced alterations of the components in the anaerobic glycolytic pathway, tricarboxylic acid cycle and energy storage, that were magnified in the skeletal muscle from the oldest animals. The effect of the chronic treatment with the TRH-analogue posatireline suggests that the action of central nervous system-acting drugs could also be related to their direct influence on the muscular biochemical mechanisms related to the energy transduction.
Aging↗
Influence of aging and drug treatment on the cerebral glutathione system.
Age-related changes of the components of the glutathione system (reduced and oxidized glutathione) were evaluated in forebrains from male Wistar rats aged 5, 10, 15, 20, 25, 30 and 35 months. The trend of both forms of glutathione and the glutathione redox index markedly differs with age. Reduced glutathione increases during the first third of a rat's life and decreases thereafter. In contrast, oxidized glutathione remains relatively constant during the first half of the life-span and increases thereafter. Thus, the glutathione redox index steadily declines with age after an increase during the first third of the rat's life-span. In rats aged 10, 20 or 30 months, chronic IP treatment for two months with drugs known to modify cerebral circulation (papaverine) or the cerebral metabolism (ergot alkaloids dihydroergocristine, dihydroergocriptine) indicates that, according to the age, the cerebral glutathione system may be modified by metabolic changes rather than by circulatory events.
Aging↗
Acetylcholinesterase activity of synaptic plasma membranes during ageing: effect of L-acetylcarnitine.
A physiopathological role for acetylcholine (ACh) was hypothesized during ageing and related neurodegenerative diseases, e.g. dementia. This research was aimed to study acetylcholinesterase (AChE) activity during development and ageing of the frontal cerebral cortex of 4-, 8-, 12-, 16-, 20- and 24-month-old rats. This study was performed on synaptic plasma membranes, the specific subcellular compartment where the enzyme is located in vivo both in control animals and after in vivo acute treatment with L-acetylcarnitine. Maximum AChE activity was unaffected by age, and L-acetylcarnitine treatment increased enzyme activity in synaptic plasma membranes of 8-month-old rats. A comprehensive analysis of these results suggests: (a) the observed alterations in protein can substantially affect neurochemical data if results are presented as specific activities per unit protein; (b) energy metabolism plays the major role in the disturbed ACh metabolism during ageing and (c) the understanding of the mode of action of L-acetylcarnitine in treatment of dementia.
Acetylcarnitine↗
Effect of phenobarbital on cerebral energy state and metabolism. Enzymatic activities.
The changes induced by phenobarbital in cerebral enzymatic activities of the Krebs' cycle (citrate synthase, malate dehydrogenase) and electron transfer chain (total NADH-cytochrome c reductase and cytochrome oxidase) were studied. In addition, the activity of lactate dehydrogenase of acetylcholine esterase and of glutamate dehydrogenase was also studied. These enzymatic activities were evaluated in the homogenate in toto and in a crude mitochondrial fraction from rat brain. The modifications in some of these activities indicate that several new metabolic situations occur in brain tissue after phenobarbital treatment.
Animals↗
Natural distribution and occurrence of coenzyme Q homologues.
The knowledge of coenzyme Q levels in tissues, organs, and subcellular compartments is of outstanding interest. A wide amount of data regarding coenzyme Q distribution and occurrence was collected in the last decades; nevertheless the data are often hard to compare because of the different extraction methods and different analytical techniques used. We have undertaken a systematic study for detecting the ubiquinone content in subcellular compartments, cells, and whole-tissue homogenates by a previously standardized HPLC method performed after an extraction procedure identical for all samples. It was confirmed that the major coenzyme Q homologue in rat tissues is coenzyme Q9; however, it was pointed out that all the rodents samples tested contain more than one coenzyme Q homologue. The coenzyme Q homologue distribution is tissue dependent with relatively high coenzyme Q10 content in brain mitochondria, irrespective of the rat strain used. There is no constant relationship of the coenzyme Q content in mitochondria and microsomes fractions. Most organisms tested (including other mammals, bird and fish specimens) have only coenzyme Q10, while the protozoan Tetrahymena pyriformis contains only coenzyme Q8.
Animals↗
[The influence of aging on cerebral energy metabolism following post-hypoglycemic recovery in the rat. Pharmacologic application].
Influence of aging on cerebral energetic metabolism was evaluated during and after severe hypoglycemia in rats respectively 20 (adults), 60 (matures) or 100 (senescents) week-old. Cerebral content of carbohydrates, amino-acids, ammonia, ATP, ADP, AMP, creatine phosphate and creatine was analysed after 20 min insulin induced hypoglycemia and after 20 min hypoglycemic recovery induced by glucose infusion. In the rats of different ages tested, effect of raubasine (0.85 mg X kg-1 i.p. and i.v.), almitrine (2.68 mg X kg-1 i.p. and i.v.) and association almitrine plus raubasine (at the same doses) on post-hypoglycemic recovery was tested. Aging does not affect the cerebral metabolic disorders occurring in severe hypoglycemia, but rather the metabolic changes during the post-hypoglycemic restitution. In fact there is lower restitution of the concentrations of cerebral cortical metabolites in older rats: the concentrations of many amino-acids and adenylate nucleotides remains largely abnormal. Compared with saline treated post-hypoglycemic rats, raubasine decreases by 15 to 20% cerebral glucose and pyruvate contents in "adults" and "matures" rats and by 10 to 15% glutamate content in rat of different ages tested. Almitrine decreases by 20% cerebral glucose concentration in "matures" and "senescent" rats. In this latter group, almitrine decreases lactate and ammonium contents and increases by 23% glutamine level. In rats of all ages that were submitted to 20 min insulin induced hypoglycemia followed by 20 min glucose induced post-hypoglycemic recovery, the association almitrine plus raubasine decreases by 20 to 30% cerebral glucose, pyruvate and lactate contents and decreases by 15% glutamate. In older brains the association almitrine plus raubasine decreases by 50% cerebral content in ammonium and concomitantly induces an equivalent increase in glutamine content. The effect of the combination almitrine plus raubasine is characterized by an increase in rate of metabolic recovery process in all ages tested.
Aging↗