Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyotrophic lateral sclerosis is a fatal paralytic disorder of unknown cause. Recent evidence implicated the role of free radicals in the death of motor neurons in this disease. To investigate this hypothesis further, we measured the activity of the main free radical scavenging enzymes copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase in postmortem brain samples from 9 patients with sporadic amyotrophic lateral sclerosis and from 9 control subjects. We examined samples from the precentral gyrus of the cerebral cortex, a region affected in amyotrophic lateral sclerosis, and from the cerebellar cortex, a region not affected. The two groups did not differ in age or postmortem delay. In the precentral gyrus from amyotrophic lateral sclerosis samples, glutathione peroxidase activity as measured by spectrophotometric assay (13.8 +/- 2.6 nmol/min/mg protein [mean +/- standard error of mean]) was reduced significantly compared to the activity in the precentral gyrus from control samples (22.7 +/- 0.5 nmol/min/mg protein). In contrast, glutathione peroxidase activity was not significantly altered in the cerebellar cortex from amyotrophic lateral sclerosis patients compared to controls. Copper/zinc superoxide dismutase, manganese superoxide dismutase (corrected or not corrected for citrate synthase), and catalase were not significantly altered in the precentral gyrus or cerebellar cortex in the patient samples. This study indicated that glutathione peroxidase activity is reduced in a brain region affected in amyotrophic lateral sclerosis, thus suggesting that free radicals may be implicated in the pathogenesis of the disease.
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PMID:Brain superoxide dismutase, catalase, and glutathione peroxidase activities in amyotrophic lateral sclerosis. 896 46

Thiobarbituric acid reactant substances (TBARs) content, and the activities of glucose-6-phosphate dehydrogenase (G6PDh), citrate synthase (CS), Cu/Zn- and Mn-superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) were measured in the lymphoid organs (thymus, spleen, and mesenteric lymph nodes (MLN)) and skeletal muscles (gastrocnemius and soleus) of adrenodemedullated (ADM) rats. The results were compared with those obtained for sham-operated rats. TBARs content was reduced by adrenodemedullation in the lymphoid organs (MLN) (28%), thymus (40%) and spleen (42%)) and gastrocnemius muscle (67%). G6PDh activity was enhanced in the MLN (69%) and reduced in the spleen (28%) and soleus muscle (75%). CS activity was reduced in all tissues (MLN (75%), spleen (71%), gastrocnemius (61%) and soleus (43%)), except in the thymus which displayed an increment of 56%. Cu/Zn-SOD activity was increased in the MLN (126%), thymus (223%), spleen (80%) and gastrocnemius muscle (360%) and was reduced in the soleus muscle (31%). Mn-SOD activity was decreased in the MLN (67%) and spleen (26%) and increased in the thymus (142%), whereas catalase activity was reduced in the MLN (76%), thymus (54%) and soleus muscle (47%). It is particularly noteworthy that in ADM rats the activity of glutathione peroxidase was not detectable by the method used. These data are consistent with the possibility that epinephrine might play a role in the oxidative stress of the lymphoid organs. Whether this fact represents an important mechanism for the establishment of impaired immune function during stress remains to be elucidated.
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PMID:Changes in the TBARs content and superoxide dismutase, catalase and glutathione peroxidase activities in the lymphoid organs and skeletal muscles of adrenodemedullated rats. 969 30

The effects of endurance training on gene expression of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were investigated in type 2a and 2b skeletal muscles, as well as heart and liver, in the rat. Female Sprague-Dawley rats (4 months old, 300-320 g) were randomly divided into a trained (T, n = 11) and a control (C, n = 10) group and were pair fed a diet consisting of 66% cornstarch and 34% basal diet that contained all essential nutrients. Training was conducted on a treadmill at 25 m x min(-1), 10% grade for 2 h per day, 5 days per week for 10 weeks, resulting in a 79% (p < 0.01) increase in citrate synthase activity in the deep portion of vastus lateralis muscle (DVL, type 2a). Cu-Zn SOD activity was 35% higher (p < 0.01) in DVL of T versus C rats, and Cu-Zn SOD mRNA abundance showed a 125% increase with training (p < 0.05). Cu-Zn SOD protein content was not altered in DVL, but increased significantly (p < 0.05) in the superficial portion of vastus lateralis (type 2b) with training. Trained rats showed a 66% higher (p < 0.05) Mn SOD protein content in DVL, but Mn SOD activity and mRNA abundance were not affected. Training also significantly increased GPX activity by 62% (p < 0.05), without changing its mRNA abundance, in the DVL. Heart and liver showed a 112 and 58% increase (p < 0.01) in Cu-Zn SOD mRNA abundance with training, respectively, but no other training adaptation was detected. These data indicate that endurance training can promote gene expression of muscle antioxidant enzymes in a fiber-specific manner. Training appears to upregulate Cu-Zn SOD mRNA abundance in a number of aerobic tissues, whereas Mn SOD and GPX induction observed in DVL may occur at the post-transcriptional levels.
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PMID:Endurance training alters antioxidant enzyme gene expression in rat skeletal muscle. 1032 36

The effects of endurance training on the enzyme activity, protein content, and mRNA abundance of Mn and CuZn superoxide dismutase (SOD) were studied in various phenotypes of rat skeletal muscle. Female Sprague-Dawley rats were randomly divided into trained (T, n = 8) and untrained (U, n = 8) groups. Training, consisting of treadmill running at 27 m/min and 12% grade for 2 h/day, 5 days/wk for 10 wk, significantly increased citrate synthase activity (P < 0. 01) in the type I (soleus), type IIa (deep vastus lateralis, DVL), and mixed type II (plantaris) muscles but not in type IIb (superficial vastus lateralis, SVL) muscle. Mitochondrial (Mn) SOD activity was elevated by 80% (P < 0.05) with training in DVL. SVL and plantaris muscle in T rats showed 54 and 42% higher pooled immunoreactive Mn SOD protein content, respectively, than those in U rats. However, no change in Mn SOD mRNA level was found in any of the muscles. CuZn SOD activity, protein content, and mRNA level in general were not affected by training, except for a 160% increase in pooled CuZn SOD protein in SVL. Training also significantly increased glutathione peroxidase and catalase activities (P < 0.05), but only in DVL muscle. These data indicate that training adaptations of Mn SOD and other antioxidant enzymes occur primarily in type IIa fibers, probably as a result of enhanced free radical generation and modest antioxidant capacity. Differential training responses of mRNA, enzyme protein, and activity suggest that separate cellular signals may control pre- and posttranslational regulation of SOD.
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PMID:Superoxide dismutase gene expression in skeletal muscle: fiber-specific adaptation to endurance training. 1048 4

The effect of the induction of i-NOS in primary glial cultures was studied with respect to the protein levels of reactive oxygen species (ROS) scavenging enzymes and the cytotoxicity of nitric oxide (.NO) formation at different levels of artificially generated superoxide. Stimulation of the cultures by bacterial lipopolysaccharides and gamma-interferon resulted in an induction of i-NOS exclusively in microglial cells. Among the ROS scavenging enzymes superoxide dismutase (Cu/Zn- and Mn-isoform), glutathione peroxidase and catalase only mitochondrial Mn-SOD was found to be upregulated in the course of i-NOS induction (Western blots). Although .NO formation did not affect cell viability at physiological levels of superoxide over a time period of 4 days, it caused an oxidative load particularly in microglial cells as observed by monitoring the oxidation of dichloro-dihydrofluorescein, an indicator for the formation of peroxynitrite and ROS. Elevated levels of superoxide, generated either intracellularly by paraquat or extracellularly via xanthine oxidase and hypoxanthine, resulted dose-dependently in a larger decline of cell viability in the .NO forming cultures compared to controls (release of lactate dehydrogenase, citrate synthase, stainability by propidium iodide, and tetramethylrhodamine). NOS-inhibitors reduced the degree of cell damage to that seen for control cultures, indicating an ONOO--/.NO mediated mechanism of cell damage. Our data support the concept that i-NOS catalyzed .NO-formation leads to an ONOO--mediated increased oxidative load. At physiological levels of superoxide and within a wide range of higher superoxide levels this nitrosative stress is well balanced in cultured glial cells by protective mechanisms.
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PMID:Peroxynitrite mediated damage and lowered superoxide tolerance in primary cortical glial cultures after induction of the inducible isoform of NOS. 1049 18

Oxygen, while being an obligate fuel for aerobic life, has been shown to be toxic through its deleterious reactive species, which can cause oxidative stress and lead ultimately to cell and organism death. In marine organisms, reactive oxygen species (ROS), such as the superoxide anion and hydrogen peroxide, are generated within respiring cells and tissues and also by photochemical processes in sea water. Considering both the reduced metabolic rate of nektonic organisms thriving in the deep sea and the physico-chemical conditions of this dark, poorly oxygenated environment, the meso- and bathypelagic waters of the oceans might be considered as refuges against oxidative dangers. This hypothesis prompted us to investigate the activities of the three essential enzymes (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPX) constitutive of the antioxidative arsenal of cells in the tissues of 16 species of meso- and bathypelagic fishes occurring between the surface and a depth of 1300 m. While enzymatic activities were detected in all tissues from all species, the levels of SOD and GPX decreased in parallel with the exponential reduction in the metabolic activity as estimated by citrate synthase activity. In contrast, CAT was affected neither by the metabolic activity nor by the depth of occurrence of the fishes. High levels of metabolic and antioxidative enzymes were detected in the light organs of bioluminescent species. The adjustment of the activity of SOD and GPX to the decreased metabolic activity associated with deep-sea living suggests that these antioxidative defense mechanisms are used primarily against metabolically produced ROS, whereas the maintenance of CAT activity throughout all depths could be indicative of another role. The possible reasons for the occurrence of such a reduced antioxidative arsenal in deep-sea species are discussed.
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PMID:Reduced enzymatic antioxidative defense in deep-sea fish. 1107 35

The elevated rate of oxygen consumption and high amount of polyunsaturated fatty acids make the central nervous system vulnerable to oxidative stress. The effect of Walker-256 tumor growth on oxi-reduction indexes in the hypothalamus (HT), cortex (CT), hippocampus (HC) and cerebellum (CB) of male Wistar rats was investigated. The presence of the tumor caused an increase in thiobarbituric acid reactant substances (TBARs) in the HT, CB and HC. Due to tumor growth, the activity of glucose-6-phosphate dehydrogenase increased in the HT and CB, whereas citrate synthase activity was reduced in the HT, CT and CB. Therefore, the potential for generation of reducing power is increased in the cytosol and decreased in the mitochondria of various brain regions of Walker-256 tumor-bearing rats. These changes occurred concomitantly with an unbalance in the brain enzymatic antioxidant system. The tumor decreased the activities of catalase in the HT and CB and of glutathione peroxidase in the HT, CB and HC, and raised the CuZn-superoxide dismutase activity in the HT, CB and HC. These combined findings indicate that Walker-256 tumor growth causes oxidative stress in the brain.
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PMID:Walker-256 tumor growth causes oxidative stress in rat brain. 1129 28

The antioxidant properties of North American ginseng (Panax quinquefolium) were investigated in young and old rats fed a ginseng-supplemented diet for 4 mo. Female Fischer 344 rats at 4 (Y, n = 38) or 22 (O, n = 25) mo of age were randomly divided into three groups and fed either a AIN-93G formula-based control diet (C) or a diet containing 0.5 g/kg (low dose, L) or 2.5 g/kg (high dose, H) dry ginseng power for 4 mo. Oxidant generation, measured with 2'7'-dichlorofluorescin (DCFH), was significantly lowered with ginseng feeding in the homogenates of heart, soleus, and the deep portion of vastus lateralis muscle (DVL) (P < 0.05) in both Y and O rats, and the effects were dose dependent. Superoxide dismutase activity was elevated in heart and DVL of H rats, and in soleus of L rats (P < 0.05). H rats showed higher glutathione peroxidase activity in DVL and soleus muscle (P < 0.05), and elevated citrate synthase activity in the heart of both age groups and DVL of Y rats (P < 0.05). Neither the H nor L diet affected age-dependent lipid peroxidation in the heart or muscle, but protein carbonyl content was attenuated with the H diet in the heart (P < 0.05) and with both the L and H diets in DVL (P < 0.01). We conclude that ginseng supplementation can prevent age-associated increase in oxidant production and oxidative protein damage in rats. These protective effects are explained in part by elevated antioxidant enzyme activities in the various tissues.
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PMID:Chronic ginseng consumption attenuates age-associated oxidative stress in rats. 1460 81

The aim of this work was to evaluate the effects of prolonged starvation and refeeding on antioxidant status and some metabolic-related parameters in common dentex (Dentex dentex) liver. Fish deprived of food for 5 weeks showed a significant increase in lipid peroxidation, measured as malondialdehyde (MDA) levels. The activity of the antioxidative enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) in starved fish significantly increased (by 42%, 22%, and 52%, respectively), whereas glutathione reductase (GR) activity was significantly depressed by 53% compared to controls. No qualitative changes in the SOD isoenzymatic pattern were detected by nondenaturing PAGE analysis, but the isoforms corresponding to CuZn-SOD I and II were enhanced in starved fish. The activity of the enzymes indicative of oxidative metabolism, beta-hydroxyacyl CoA dehydrogenase (HOAD) and citrate synthase (CS), significantly increased (by 123% and 28%, respectively), and that of glucose-6-phosphate dehydrogenase (G6PDH) was inhibited by 56%. Oxidative damage under these circumstances is reversible since all biomarkers assayed returned to control values after refeeding. Our results show that prolonged starvation leads to a pro-oxidant situation and oxidative stress despite activation of antioxidant defense mechanisms, and that inhibition of G6PDH activity might be responsible for this failure in cellular antioxidant defenses.
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PMID:Oxidative stress and antioxidant defenses after prolonged starvation in Dentex dentex liver. 1555 78

We report here that estrogen (E(2)) modulates mitochondrial function in the vasculature. Mitochondrial dysfunction is implicated in the etiology of vascular disease; thus, vasoprotection by estrogen may involve hormonal effects on the mitochondria. To test this hypothesis, mitochondria were isolated from cerebral blood vessels obtained from ovariectomized female rats, with or without E(2) replacement. Estrogen receptor-alpha (ER-alpha) was detected in mitochondria by immunoblot and confocal imaging of intact vessels. E(2) treatment in vivo increased the levels of specific proteins in cerebrovascular mitochondria, such as ER-alpha, cytochrome c, subunit IV of complex IV, and manganese superoxide dismutase, all encoded in the nuclear genome, and subunit I of complex IV, encoded in the mitochondrial genome. Levels of glutathione peroxidase-1 and catalase, however, were not affected. Functional assays of mitochondrial citrate synthase and complex IV, key rate-limiting steps in energy production, showed that E(2) treatment increased enzyme activity. In contrast, mitochondrial production of hydrogen peroxide was decreased in vessels from E(2)-treated animals. In vitro incubation of cerebral vessels with 10 nM 17beta-estradiol for 18 h also elevated levels of mitochondrial cytochrome c. This effect was blocked by the estrogen receptor antagonist fulvestrant (ICI-182,780, Faslodex) but was unaffected by inhibitors of nitric-oxide synthase or phosphoinositide-3-kinase. Nuclear respiratory factor-1 protein, a primary regulator of nuclear gene-encoded mitochondrial genes, was significantly increased by long-term estrogen treatment in vivo. In summary, these novel findings suggest that vascular protection by E(2) is mediated, in part, by modulation of mitochondrial function, resulting in greater energy-producing capacity and decreased reactive oxygen species production.
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PMID:Estrogen increases mitochondrial efficiency and reduces oxidative stress in cerebral blood vessels. 1599 67


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