Changes In Succinate Dehydrogenase Activity Research Articles

Uridine as a Regulator of Functional and Ultrastructural Changes in the Brain of Rats in a Model of 6-OHDA-Induced Parkinson's Disease.

Using a model of Parkinson's disease (PD) induced by the bilateral injection of neurotoxin 6-hydroxydopamine (6-OHDA) into rat brain substantia nigra (SN), we showed uridine to exert a protective effect associated with activation of the mitochondrial ATP-dependent potassium (mitoK-ATP) channel. Injection of 4 µg neurotoxin evoked a 70% decrease in the time the experimental animal spent on the rod in the RotaRod test, an increase in the amount of lipid peroxides in blood serum and cerebral-cortex mitochondria and the rate of reactive oxygen species formation, and a decrease in Ca2+ retention in mitochondria. Herewith, lymphocytes featured an increase in the activity of lactate dehydrogenase, a cytosolic enzyme of glycolysis, without changes in succinate-dehydrogenase activity. Structural changes occurring in the SN and striatum manifested themselves in the destruction of mitochondria, degeneration of neurons and synapses, and stratification of myelin sheaths in them. Subcutaneous injections of 30 µg/kg uridine for 22 days restored the neurotoxin-induced changes in these parameters to levels close to the control. 5-Hydroxydecanoate (5 mg/kg), a specific mitoK-ATP channel inhibitor, eliminated the beneficial effect of uridine for almost all characteristics tested, indicating the involvement of the mitoK-ATP channel in the protective effect of uridine. The mechanism of the protective effect of uridine and its therapeutic applications for the prevention and treatment of PD are discussed.

Blunted angiogenesis and hypertrophy are associated with increased fatigue resistance and unchanged aerobic capacity in old overloaded mouse muscle.

We hypothesize that the attenuated hypertrophic response in old mouse muscle is (1) partly due to a reduced capillarization and angiogenesis, which is (2) accompanied by a reduced oxidative capacity and fatigue resistance in old control and overloaded muscles, that (3) can be rescued by the antioxidant resveratrol. To investigate this, the hypertrophic response, capillarization, oxidative capacity, and fatigue resistance of m. plantaris were compared in 9- and 25-month-old non-treated and 25-month-old resveratrol-treated mice. Overload increased the local capillary-to-fiber ratio less in old (15 %) than in adult (59 %) muscle (P < 0.05). Although muscles of old mice had a higher succinate dehydrogenase (SDH) activity (P < 0.05) and a slower fiber type profile (P < 0.05), the isometric fatigue resistance was similar in 9- and 25-month-old mice. In both age groups, the fatigue resistance was increased to the same extent after overload (P < 0.01), without a significant change in SDH activity, but an increased capillary density (P < 0.05). Attenuated angiogenesis during overload may contribute to the attenuated hypertrophic response in old age. Neither was rescued by resveratrol supplementation. Changes in fatigue resistance with overload and aging were dissociated from changes in SDH activity, but paralleled those in capillarization. This suggests that capillarization plays a more important role in fatigue resistance than oxidative capacity.

Effects of Concurrent Training on Oxidative Capacity in Rat Gastrocnemius Muscle

Training for improvement of oxidative capacity of muscle fibers may be attenuated when concurrently training for peak power. However, because of fiber type-specific recruitment, such attenuation may only account for high-oxidative muscle fibers. Here, we investigate the effects of concurrent training on oxidative capacity (as measured by succinate dehydrogenase (SDH) activity) by using task-specific recruitment of the high- and low-oxidative compartment of rat medial gastrocnemius muscle (GM). Forty rats were subjected to 6 wk of peak power training (PT, n = 10), endurance training (ET, n = 10), concurrent peak power and endurance training (PET, n = 10), or no training (control, n = 10). SDH activity, mRNA expression of SDH, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), receptor-interacting protein 140, and BCL2/adenovirus E1B 19 kDa-interacting protein 3 as well as PGC-1α protein levels were analyzed in the low- and high-oxidative region of the GM. In the low-oxidative compartment, PT and PET induced a 30% decrease in SDH activity of Type IIB fibers compared with controls and ET (P < 0.001) without changes in mRNA or protein levels. In the high-oxidative compartment, after ET, SDH mRNA levels were 42% higher and RIP140 mRNA levels 33% lower compared with controls, which did not result in changes in SDH activity. These results indicate that in compartmentalized rat GM, peak power on top of endurance training attenuated transcription of mRNA for mitochondrial proteins in high-oxidative muscle fibers. In low-oxidative Type IIB fibers, peak power training substantially decreased SDH activity, which was not related to lower SDH mRNA levels. It is concluded that PT and PET enhanced mitochondrial degradation in the low-oxidative compartment of rat GM.

Insulin-like effect of the phosphodiesterase type 5 inhibitor tadalafil onto male human skeletal muscle cells.

Phosphodiesterase type 5 inhibitors (PDE5i), widely used to treat male erectile dysfunction, seem to counteract insulin resistance (IR) in animals and humans. IR, primarily manifest in peripheral tissues and particularly in skeletal muscle, is due to impaired insulin signal transduction. Investigators have been focusing onto intracellular defects responsible for IR to identify suitable pharmacological tools targeted toward the specific defects. Albeit some effects of PDE5i have been reported onto animal muscular tissues or cells, whether and how they might affect metabolic processes directly in human skeletal muscle still remains unclear. We aimed to investigate in human fetal skeletal muscle cells (Hfsmc) the effect of tadalafil, one of PDE5i, onto some intracellular factors involved in response to insulin, such as ras-raf mitogen activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PKB/Akt), glycogen synthase kinase 3β (GSK-3β), and the transcriptional factor c-Myc; proliferation rate; lactate (lact) and free fatty acid (ffa) release; activity of citrate synthase (CS) and succinate dehydrogenase (SDH), both enzymes of Kreb's cycle; PDE5 gene expression. Western blot analysis, enzyme-linked immunosorbent assay, enzymatic assays, cell count, MTT assay and Real Time PCR were performed in Hfsmc with and without tadalafil. In Hfsmc tadalafil affected the insulin-related intracellular cascade, by increasing MAPK, PKB/Akt, GSK-3β phosphorylation and c-Myc expression. ffa release and CS activity also significantly increased, with no changes in SDH activity and lact release. Tadalafil, like insulin, targeted part of the machinery dedicated to energy management and metabolic control in human skeletal muscle cells.

Increased activity of mitochondrial respiratory chain complex in noise-damaged rat cochlea

Conclusion: Functional changes of mitochondrial respiratory chain (MRC) and hearing threshold shifts were observed after noise exposure and the pattern was different depending on the extent of the noise damage. Objectives: The aim of this study was to reveal any functional changes of the MRC enzyme in outer hair cells after noise damage. Methods: Sprague-Dawley rats were used and divided into three groups including normal control group and noise exposure for 1 h and 5 h. White band noise was used with 120 dB SPL. We measured hearing threshold and activity of succinate dehydrogenase (SDH) before noise exposure, and immediately and 1, 3, 7, and 14 days after noise exposure in each group. Immunostaining using monoclonal anti-MRC complex V subunit α was performed. Transmission electron microscopy (TEM) was carried out. Results: The hearing threshold level changed depending on the exposure time in both the noise-exposed groups. In the 1 h group, hearing was improved after 1 day, and in the 5 h group, hearing was measured after 7 days. Changes in SDH activity were observed at the third day in the 1 h group and at the seventh day in the 5 h group. The expression level of MRC complex V was increased after noise exposure. TEM showed mitochondrial damage.

Changes in succinate dehydrogenase activity in various parts of the brain during combined exposure to vibration and licorice root

Data obtained in the studies reported here provide evidence that during exposure to vibration for 30 days, feeding with licorice root significantly increases the activity of the anaerobic respiration enzyme succinate dehydrogenase (SDH) in the cerebral cortex, while activity in the subcortex, conversely, decreases. Combined treatment for 30 days with licorice root and vibration after a preliminary 30-day period of feeding with licorice root resulted in high SDH activity in all the structures studied, improving brain energy supply and metabolism and ameliorating the effect of vibration.

Regional Distribution Of SDH In Single Muscle Fibres After Training In Endurance Cyclists

Previous research has shown that two populations of mitochondria with different metabolic properties exist in human skeletal muscle. Recent research has shown that the regional distribution of succinate dehydrogenase (SDH) in single muscle fibres is altered with moderate intensity endurance training. Based on this information, we tested the hypothesis that the regional distribution of mitochondria would be altered following sustained high intensity endurance training. PURPOSE The purpose of this study was to examine the changes in the subsarcolemmal (SSM) and intermyofibrillar (IMF) mitochondria as represented by changes in SDH activity. METHODS Eight (2 female, 6 male) trained cyclists (VO2max = 60.7 mL.kg−1·min−1) performed eight weeks of high intensity endurance training for 60 minutes × 5d.wk−1 at 80–85% VO2max. Pre- and post-training muscle biopsy samples were taken from the vastus lateralis, and then immediately frozen in isopentane until analyzed histochemically for SDH activity. Frozen tissue sections (6μm) were incubated and then analyzed using a computer-enhanced image analysis system which digitized selected fibres (18–75) to represent SDH activity as an optical density. Concentric rings (pixel width 0.75μm) were partitioned from the outside layer (SSM, <5.25μm) to the inside layer (IMF, > 6.00μm). Based on myofibrillar ATPase staining, Type I and Type II fibres were identified. RESULTS The results showed that significant changes (ANOVA, p < 0.05) occurred for all analyses performed, both pre- vs. post-training for fibre types, and between SSM and IMF mitochondria. SDH activity increased significantly in Type II (71.7%) vs. Type I (28.3%) over training. The greatest increases in the mitochondrial activity occurred in the SSM (54.6%) vs. IMF (45.4%). However, the greatest increase in SDH activity occurrred in the IMF mitochondria of Type II fibres (39.7%). CONCLUSIONS These data demonstrated that high intensity endurance training can elicit selective adaptations in the metabolic profile of different fibre types in single muscle fibres, and that regional differences in SDH activity can occur.

Effect of weight loss on muscle fiber type, fiber size, capillarity, and succinate dehydrogenase activity in humans.

To examine the effects of weight loss on muscle oxidative properties, nine obese subjects (body mass index, 34 +/- 1.5) had muscle biopsies before and after weight loss and weight stabilization. Weight loss ranged from 13-32 kg and represented 20.8 +/- 2.1% of initial weight. After weight loss, there was no change in the proportions of oxidative (type I and type IIa) fibers and also no change in mean fiber cross-sectional area, whereas there was a small, but significant, decrease in the relative interstitial space (P < 0.05). However, weight loss resulted in a 32 +/- 6% (mean +/- SEM) increase in capillary/fiber ratio and a 54% increase in capillary density (P < 0.05). In addition, there was a 41 +/- 13% increase in succinate dehydrogenase (SDH) activity (P < 0.05). This increase in muscle capillarization and SDH activity was seen in all fiber types, even the relatively lower oxidative type IIx fibers. There was a strong correlation between the change in capillary/fiber ratio and the change in SDH activity (r = 0.82; P < 0.02). Thus, weight loss resulted in no change in muscle fiber type or cross-sectional area, but produced increases in capillary/fiber ratio, capillary density, and SDH activity, suggesting an increase in muscle oxidative capacity.

Metabolic and phenotypic adaptations of diaphragm muscle fibers with inactivation.

We hypothesized that metabolic adaptations to muscle inactivity are most pronounced when neurotrophic influence is disrupted. In rat diaphragm muscle (Dia(m)), 2 wk of unilateral denervation or tetrodotoxin nerve blockade resulted in a reduction in succinate dehydrogenase (SDH) activity of type I, IIa, and IIx fibers (approximately 50, 70, and 24%, respectively) and a decrease in SDH variability among fibers (approximately 63%). In contrast, inactivity induced by spinal cord hemisection at C2 (ST) resulted in much less change in SDH activity of type I and IIa fibers (approximately 27 and 24%, respectively) and only an approximately 30% reduction in SDH variability among fibers. Actomyosin adenosinetriphosphatase (ATPase) activities of type I, IIx, and IIb fibers in denervated and tetrodotoxin-treated Dia(m) were reduced by approximately 20, 45, and 60%, respectively, and actomyosin ATPase variability among fibers was approximately 60% lower. In contrast, only actomyosin ATPase activity of type IIb fibers was reduced (approximately 20%) in ST Dia(m). These results suggest that disruption of neurotrophic influence has a greater impact on muscle fiber metabolic properties than inactivity per se.

Norepinephrine does not stimulate protein and UCP synthesis in brown adipocytes of golden Syrian hamsters

Hamster brown adipocytes were incubated for up to 24 h with or without norepinephrine (NE) in Dulbecco's modified Eagle's medium supplemented with bovine serum albumin, calf serum, and antibiotics. Brown fat cells were viable for 24 h as defined by their ability to respond to NE by a 10-fold increase in oxygen consumption. However, prolonged exposure of the cells to NE led to a decline in NE-stimulated rates of O2 consumption, which was not the result of loss of cell thermogenic capacity. Brown fat cells incubated for 24 h with or without NE showed no significant change in succinate dehydrogenase activity or uncoupling protein (UCP) content. However, cell recovery after 24 h was significantly reduced in the absence of NE. In brown adipocytes isolated from rat, NE increased [35S]methionine incorporation into cell proteins and UCP. In contrast, [35S]methionine incorporation in hamster brown adipocyte proteins and UCP was greater than in rat brown fat cells and was not increased by NE. These results indicate that although NE may be required for cell survival, it does not stimulate protein and UCP synthesis in hamster brown fat cells.

Diaphragm capillarity and oxidative capacity during postnatal development

In the cat diaphragm, fiber capillarity, cross-sectional area, and succinate dehydrogenase (SDH) activity were measured across the first 6 wk of postnatal development. Fibers were classified as type I, IIa, IIb, or IIc on the basis of staining for myofibrillar adenosinetriphosphatase (ATPase). Capillaries were identified in sections stained for ATPase at pH 4.2. Fiber cross-sectional areas and SDH activities were quantified using an image-processing system. During postnatal development, the proportions of type I fibers increased while type II fibers decreased. At birth, all type II fibers were IIc. From the 1st to the 2nd postnatal wk, the proportion of type IIc fibers decreased while the numbers of IIa and IIb increased. Thereafter the proportion of type IIb fibers continued to increase while the number of IIa steadily declined. At birth, capillarity, cross-sectional areas, and SDH activities of type I and II fibers were low compared with other postnatal age groups. Fiber cross-sectional areas increased progressively with age. The number of capillaries surrounding type I and II fibers increased markedly by the 2nd wk and then continued to increase at a slower rate. The number of capillaries per fiber area reached a peak by the 2nd wk and then declined as fiber cross-sectional area increased. Postnatal changes in capillarity depended on fiber type, being greatest in IIb. SDH activities of type I and II fibers were initially low during the first 2 postnatal wk and then peaked by the 3rd wk. After the 6th wk, fiber SDH activities decreased to adult values. Among the type II fibers, IIb showed the greatest change in SDH activity during early postnatal development.

Developmental changes in succinate dehydrogenase activity in muscle fibers from normal and dystrophic mice

The question of whether or not the development of dystrophic muscles is similar to that of normal muscles, prior to the manifestations of the symptoms of the disease, is investigated here. The developmental change in the activity of succinate dehydrogenase was therefore measured in individual fibers of prospectively dystrophic muscles from 10- to 28-day-old mice (strain C57Bl 6J dy2j) and compared with that of muscles from normal mice of the same age. It was found that up to 10 days of age, muscle fibers from normal and prospective dystrophic animals had low succinate dehydrogenase activities, and were all more or less uniform. Thereafter in the normal muscle the overall activity of the enzyme increased and the fibers became more heterogeneous with age. By 21 days the extensor digitorum longus muscle resembled that of the adult. At that time, fibers from prospectively dystrophic muscles had lower succinate dehydrogenase activities and were more homogeneous. Thus fibers from prospectively dystrophic muscles fail to achieve their adult characteristics by 21 days. On the basis of these results, it is suggested that muscle maturation is retarded in dystrophic animals.

The effect of sugar mill effluent on enzyme activities of rice seedlings

The effect of sugar mill effluent on the activities of peroxidase, amylase, and nitrate reductase of rice (Oryza Sativa L. C.V. Mushoori) seedlings have been investigated. In addition, an attempt was also made to investigate effluent-induced changes in the activities of mitochondrial enzymes, such as succinate dehydrogenase, during germination of rice seedlings. The effects were studied in relation to both concentration of effluent and time of exposure. The activity of all enzymes tested, except succinate dehydrogenase, decreased during effluent treatment. A marked increase in succinate dehydrogenase activity was noticed at various concentrations of effluent treatment. When time-dependent changes in succinate dehydrogenase activity were followed a nearly threefold increase was found with 12 hr of treatment after which a rapid loss was noticed. A correlation was established between the retardation of growth and development of effluent-treated rice seedlings with the activities of some key enzymes regulating growth and development.

Acute and chronic hypoxia in rats. I. Effect on organismic respiration, mitochondrial protein mass in liver and succinic dehydrogenase activity in liver, kidney and heart.

The objective of this investigation was to characterize organismic, organ and mitochondrial alterations in rats over the course of 27 days at 0.4 atm. In the adjustment phase (day 1 through 5) a significant decrease in systemic oxygen uptake and body weight (23% of pre-altitude values) occurred. In the acclimating state (day 7 to 27) body weight was regained but oxygen consumption remained depressed. Hematocrit increased hyperbolically from 45% in 0-day rats to 79% in 27-day rats. Liver, kidney and heart weights and total organ protein paralleled the changes observed in body weight. Total organ succinic dehydrogenase activity showed a wave-like oscillation for liver and kidney; activity was decreased in both organs by day 5, showed a transient but significant increase on days 16 through 18 and a return to diminished activity on day 27. Succinic dehydrogenase activity for heart became depressed in the adjustment phase but showed a stable level comparable to pre-altitude values in the accliminating phase, days 7 through 27. Liver mitochondrial protein mass was unchanged from pre-altitude values on days 5 and 27 even though succinic dehydrogenase activity was significantly depressed. Therefore, the changes in succinic dehydrogenase activity are not representative of altered mitochondrial mass but suggest that mitochondrial function was altered.

Biochemical changes associated with toxic exposrues to polytetrafluoroethylene pyrolysis products.

Abstract Rats were exposed to the products of pyrolysis of polytetrafluoroethylene (PTFE) containing hydrolyzable fluoride equivalent to 50 ppm COF2 for one hour daily. After one exposure, urinary excretion of fluoride was four times normal. Weight loss of exposed animals indicated inhibition of metabolism. Changes in succinic dehydrogenase activity in vivo correlated with exposure to pyrolysis products of PTFE and with urinary fluoride concentrations. Toxic effects of daily sublethal exposures were found to be cumulative. The metabolic inhibition observed was reversible. The toxic syndrome of daily inhalation of pyrolysis products of PTFE is compatible with descriptions of fluoride poisoning.

Relative resistance to dystrophy of slow skeletal muscle of the mouse.

Relative resistance to dystrophy of slow skeletal muscle of the mouse.

SUCCINIC DEHYDROGENASE IN PIGEON PECTORALIS DURING DISUSE ATROPHY.

Quantitative and histochemical changes in succinic dehydrogenase activity in pigeon breast muscle was studied during one to sixty days of disuse after immobilization of the wings. Muscle enzyme activity was found to decrease from the first day, reaching its lowest level after seven days. Histochemical observations on red and white muscle fibers showed that after seven days atrophy, the majority of red fibers had lower enzyme activity; a few others showed higher activity. In white fibers on the other hand, a uniform increase over normal in enzyme activity and mitochondrial number was seen. These changes in the two types of fibers were less conspicuous during the later stages of atrophy. Thus the general level of oxidative metabolism in muscle as a whole was lowered in spite of the slight increase in level of SDH in white fibers. It is suggested that in both red and white fibers there was a shift, of aerobic to anaerobic metabolism, or vice versa.

Changes in Succinic Dehydrogenase Activity and Fatty Acid Composition of Rat Liver Mitochondria in Essential Fatty Acid Deficiency

The effects of feeding diets containing corn oil, coconut oil, tuna oil, or no fat on the sequence of development of growth inhibition and altered mitochondrial fatty acid compositions and succinic dehydrogenase activities were studied. The mitochondrial succinic dehydrogenase activities of rats fed tuna oil were higher than those of the control (corn oil) rats, but lower than those of the other EFA-deficient rats throughout the experiment. Suggestive differences between control and deficient mitochondria were noted after one week of the experiment and were marked after 2 weeks. The exposure to water, the addition of calcium ion, or the addition of snake venom elevated the mitochondrial succinic dehydrogenase activities, and eliminated or reduced the differences between the control and EFA-deficient rats. The appearance of eicosatrienoic acid and a reduction of arachidonic and linoleic acids in mitochondrial lipids from the fat-free and coconut oil groups occurred within one week after initiating the experiment. The feeding of tuna oil resulted in significant amounts of a highly polyunsaturated fatty acid of calculated carbon number 23.4, which was, perhaps, eicosapentaenoic acid, but not of eicosatrienoic acid in mitochondrial lipid. The alterations of mitochondrial fatty acid composition in EFA deficiency preceded slightly the appearance of elevated succinic dehydrogenase activity.

Circadian studies on succinic dehydrogenase pantothenate and biotin of rodent adrenal.

Coenzyme A concentration and the activity of the succinic dehydrogenase system in rodent adrenals are both circadian periodic functions; both apparently can be synchronized with a 24-hour periodic regimen of alternating light and darkness. Such light-synchronized periodicity analysis reveals that circadian changes in succinic dehydrogenase activity are roughly in phase with changes in serum corticosterone and, perhaps, also in phase with the corticosterone rhythm of the adrenal itself. The circadian rhythm of adrenal CoA, in turn, shows a significant phase difference when compared either to corticosterone concentration or to the activity of the succinic dehydrogenase system. Circadian periodic changes in total biotin concentration in adrenals of rats and mice were not detected.

A Histochemical Study of the Early Stages of Carcinogenesis in Rat Liver: Localization of Fluorescent Carcinogen and Changes in Succinic Dehydrogenase Activity

A Histochemical Study of the Early Stages of Carcinogenesis in Rat Liver: Localization of Fluorescent Carcinogen and Changes in Succinic Dehydrogenase Activity