Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.15.1.1 (superoxide dismutase)
 58,858 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The extensional growth rate of wild-type 74A8 N. crassa in the presence of various concentrations of 19 amino acid analogs was measured. Seven analogs were not inhibitory at concentrations in the range of one to 10mM. Of the remaining 12 analogs, nine inhibited growth in a novel way. The kinetics of growth in the presence of these analogs at 30 degrees were characterized by seven sequential phases: (1)lag; (2) acceleration of growth rate; (3) steady-state growth rate; (4) exponential rate of decline of growth rate; (5) no growth or growth rate less than or equal to 0.1 mm h-1; (6) accleration of growth rate; and (7) steady state. At 33 degrees, phases 6 and 7 did not occur and irreparable death of the clones occurred. The mechanism by which the clones acquired resistance at 30 degrees appeared to involve a combination of physiological adaptation and cellular selection. Dietary application of either free radical scavengers or surface-active membrane 'stabilizers' alleviated or prevented the inhibition and deterioration of growth rate which occurred in the presence of the nine amino acid analogs. Culture with either 4-fluorophenylalanine or ethionine led to an increase of the activities of antioxygenic enzymes glutathione peroxidase, glutathione reductase and superoxide dismutase. The amino acid analogs that cause senescence and death of growing cells are known to be incorporated into proteins and such proteins are generally abnormal. Because a substantial fraction of cellular protein occurs in membranes and the proteins synthesized by mitochondria are exclusively intrinsic membrane proteins, we suggest that a primary consequence of errors in protein synthesis is the production of faulty membranes. The deterioration of such membranes with associated lipid autoxidation and free radical production proceeding as a chain reaction at an exponential rate may in itself contribute to the exponential rate of cellular deterioration which is characteristic of the ageing process. According to this hypothesis, dietary membrane stabilizers, free radical scavengers and antioxygenic enzymes protect cells from error catastrophy arising from the chain of events leading from membrane deterioration.
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PMID:Ageing of Neurospora crassa. IV. Induction of senescence in wild type by dietary amino acid analogs and reversal by antioxidants and membrane stabilizers. 0 15

Biochemical studies were performed on blood and lung tissue of squirrel monkeys (Saimiri sciureus) following acute exposure to 0.75 ppm ozone (O3) for 4 h/d for 4 consecutive days. One group of animals was sacrificed at the end of the last exposure day and another group was sacrificed 4 d later after the last exposure. Evidence was sought for oxidation-induced changes known to occur in rodents when high levels of O3 are inhaled. A significant increase in red blood cell membrane fragility was observed, as well as significant decreases in red blood cell glutathione and erythrocyte acetylcholinesterase; however, the red blood cell enzymes, lactic acid dehydrogenase (LDH), and glucose-6-phosphate dehydrogenase (G6PDH) were not changed significantly. Lung tissue analysis showed that lipid peroxidation was markedly increased and tissue vitamin E levels were significantly decreased. The tissue enzymes G6PDH, glutathione reductase, and LDH significantly increased in activity. No significant changes were seen in either superoxide dismutase or malic acid dehydrogenase. The results of this experiment indicate that O3, or reaction products resulting from O3-tissue interaction in the lung, pass the air-blood barrier and are capable of producing biochemical changes in blood as well as in lung tissue.
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PMID:Biochemical response of squirrel monkeys to ozone. 10 43

A recessive mutant of Neurospora crassa, called natural-death, is characterized by a decreasing clonal growth potential under all nutritional conditions and the irreversible cessation of growth. The primary molecular defect of this mutant is not known. Evidence presented here, based upon measurements of the activities and thermolabilities of several enzymes, suggests that faulty protein synthesis is probably not a cause of the senescence and death of the mutant, as suggested by Lewis and Holliday (Nature, 228 (1970) 877). Three lines of evidence indicate that lipid autoxidation and associated free radical reactions contribute to the senescence and death of this mutant: (1) The relative times before the onset of senescence and death of mutant clones in the last 40% of their chronological life-span were prolonged 2 to 3-fold by either dietary antioxidants or selenite and the total life-span was increased by 40% to 80%. These compounds also alleviated the senescent morphology and enhanced biomass production; (2) Senescing clones accumulated a green fluorescent pigment in situ, but dietary antioxidant nordihydroguaiaretic acid prevented this accumulation. The fluorescent pigment exhibited the spectral properties of lipofuscin, an end product of lipid autoxidation; (3) Relative to wild type, mycelial extracts of the mutant exhibited a 2 to 4-fold excess of activities of the antioxygenic enzymes superoxide dismutase, glutathione peroxidase and glutathione reductase. We briefly review: (1) the roles of antioxygenic enzymes and antioxidants in their protection against cellular damage from lipid autoxidation and free radical reactions; and (2) the major lines of evidence which appear to support a form of the free radical theory of ageing, encompassing the interrelated processes of membrane deterioration, lipid autoxidation and deleterious free radical reactions as the major causes of cellular deterioration.
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PMID:Ageing of Neurospora crassa. I. Evidence for the free radical theory of ageing from studies of a natural-death mutant. 13 83

Cumene hydroperoxide and tert-butyl hydroperoxide at sublethal concentrations initially prevent growth of mycelia of wild-type Neurospora crassa, but after a time the cells grow at a subnormal steady-state rate. The antioxidant nordihydroguaiaretic acid protects unadapted cells from hydroperoxide inhibition, leading to a decrease in the time before growth begins, an increase in steady-state growth rate and an increase in biomass production. The results of growth transfer experiments and enzyme measurements indicated that the acquired resistance to the hydroperoxides is physiological and most likely involves the induction of the synthesis of the antioxygenic enzymes superoxide dismutase, glutathione peroxidase and glutathione reductase. Nordihydroguaiaretic acid normalizes the levels of activities of glutathione peroxidase and glutathione reductase during culture with hydroperoxide. Molecular-induced homolysis of the hydroperoxides, a process that is induced by unsaturated fatty acids of membrane lipids, leads to lipid autoxidation in a chain reaction which produces lipid hydroperoxides, which in turn decomposes to form more free radicals. Nordihydroguaiaretic acid, a well-known free radical scavenger, probably serves to minimize hydroperoxide decomposition, lipid autoxidation and molecular damage from free radicals, whereas the coupled enzyme system glutathione peroxidase and glutathione reductase minimizes these processes by decomposing the hydroperoxides to harmless alcohols. We suggest that either free radicals derived from these processes or some consequent non-radical products may serve as the inducers of this enzyme system, rather than the hydroperoxide substrates.
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PMID:Ageing of Neurospora crassa. II. Organic hydroperoxide toxicity and the protective role of antioxidant and the antioxygenic enzymes. 13 84

Data from literature are reviewed on the gene dosage effect in human cells. Until recently the dosage effects have been distinctly shown for the genes of superoxide dismutase-1, acid phosphatase of erythrocytes, adenine phosphoribosyl transferase, glutathione reductase and nucleoside phosphorylase, located on chromosomes 21, 2, 16, 8, 14, respectively. The data are discussed in the light of problems arising from the study of the regulation of gene expression in man.
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PMID:[Effect of gene dose in human cells]. 15 56

Penicillamine, a cysteine analog with a reduced sulfhydryl group, has been used in this laboratory for the treatment of hereditary avian dystrophy. The drug delays the onset of symptoms and alleviates the debilitating aspects of the disease. To study the mechanism of drug action, the effects of penicillamine on white and red muscles of dystrophic chickens were examined with regard to the specific activities of the soluble enzymes glyceraldehyde-3-phosphate dehydrogenase, acetylphosphatase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glutathione reductase, glutathione preoxidase, superoxide dismutase, and catalase. The sulfhydryl contents of the soluble proteins and the concentration of myoglobin were also determined. In white dystrophic muscle (pectoral), there were large alterations in the various enzymatic activities compared to normal levels. In the DISCUSSION, these changes are related to the pathogenesis of the disease and to the adaptive response for protection of the severely affected fast fibers. Red dystrophic muscles (thigh) were minimally involved, in accordance with the known sparing action of the slow fiber type. The results suggested that the disease process in dystrophic muscle may be due to oxidation of the essential sulfhydryl groups of proteins. Penicillamine may produce therapeutic effects by altering the intracellular redox status, thereby promoting better regulation of enzymatic activity, membrane stability, and improved muscle function.
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PMID:Mechanism of action of penicillamine in the treatment of avian muscular dystrophy. 28 17

Neonatal rats (4--7 days old) and adult rats (approximately 80 days old) were continuously exposed to either 96--98% oxygen or air. Examination of the lungs of neonatal rats, who survived 5 days of oxygen exposure with no evidence of respiratory distress, showed significant increases in the pulmonary superoxide dismutase (SOD) activity (peak value: 144% of air-exposed controls), glutathione peroxidase (GP) activity (126%), glutathione reductase (GR) activity (122%), reduced glutathione (GSH) level (176%), and glucose-6-phosphate dehydrogenase activity (151%). Adult rats, most of whom succumbed within 3 days of oxygen exposure, did not show any significant increase in the activities of pulmonary SOD, GP, GR, and the level of GSH as compared to the air-exposed adult animals. Glucose-6-phosphate dehydrogenase was significantly elevated in the 72-hr oxygen-exposed adult rats. It is concluded that increases in the lung complement of SOD, GR, GP, and GSH in the neonatal rat during oxygen challenge may provide the mechanism(s) for their increased tolerance to hyperoxia-induced lung injury as compared to the adults.
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PMID:Oxygen toxicity: comparison of lung biochemical responses in neonatal and adult rats. 64 79

Aspirin (ASA), indomethacin (IND), hydrocortisone (HYC) or 0.25% agar (control) were administered (p.o.) daily to rats for 5 days. Following drug pretreatments, the activities of cytosolic superoxide dismutase (SOD), glutathione peroxidase (GP) and glutathione reductase (GR) were elevated 30-70%, 5-25% and 8-25%, respectively. In a second experiment, rats pretreated as above were injected (ip) on the 5th day with paraquat (PQ) (29 mg/kg). Rats in each group expired more ethane 2 hours after PQ injection. After 22 hours, expired ethane returned to zero time levels. All control rats died within 48 hours after PQ injection. At the end of 48 hours, rats pretreated with ASA, IND, or HYC demonstrated survival rates of 13%, 31%, and 47%, respectively. PQ injection produces marked elevations of SOD (82%), GP (328%), and GR (36%) in the lungs of PQ-injected controls rats over non-PQ injected controls. Elevation of these enzymes were also noted in drug-treated rats after PQ injection but at values less than PQ-injected controls. Anti-inflammatory drugs were tested in rat liver homogenates for their ability to inhibit thiobarbituric acid (TBA) reactive product formation. Only the addition of HYC resulted in a decrease formation of TBA-reactive products. Thus in vitro studies suggest that the antiinflammatory drugs tested, other than HYC, may have other mechanisms of actions in addition to inhibition of lipid peroxides.
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PMID:Effect of pretreatment with antiinflammatory agents on paraquat toxicity in the rat. 87 7

In studies directed at determining the activities of selected enzymes in lung tissue after in vivo exposure to hyperoxia, 70-day-old rats were exposed to 85% or 90% O2 for 1-14 days. After 7 days of exposure to 90% O2 (1atm), superoxide dismutase activities in mitochondrial and cytosolic fractions increased, respectively, to 245 and 145% of control; glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities increased, respectively, to 317, 175, and 413% of control. The levels of reduced glutathione and total nonprotein sulfhydryl compounds were elevated to 195% and 365% of control. Similar changes were observed in rats exposed to 85% O2 for up to 14 days, but to a lesser degree. The changes are interpreted as a reflection of the overall magnitude of oxidant-induced lung injury-reparative processes. The results suggest that hyperoxia induces an increase in lung "antioxidant" defense capabilities. This apparent adaptive response may be important in decreasing the susceptibility of lung tissue to continued O2 toxicity.
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PMID:Oxygen toxicity: augmentation of antioxidant defense mechanisms in rat lung. 127 87

The effects of verapamil (Isoptin Knoll) and calcium glubionate (Calcium Polfa) were studied on the generation of free radicals and activity of anti-oxidant enzymes in rat's gastric mucosa following the oral administration of 50% ethyl alcohol. Ethanol in this concentration caused injury to gastric mucosa as well increased the levels of peroxidation products (malonyl dialdehyde, hydroperoxides and conjugated dienes); at the same time a decreased enzyme activity was observed (superoxide dismutase, peroxidase, glutathione peroxidase, glutathione reductase, catalase). Verapamil administered before ethanol increased the ulcerogenic activity of alcohol, increased the activity of the studied antioxidant enzymes (except catalase) and caused the decrease in the levels of peroxidation products in gastric mucosa. Calcium glubionate increased the enzyme activity and showed some protective effect on gastric mucosa.
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PMID:The effect of calcium ions on the intensity of peroxidation processes and the severity of ethanol-induced injury to the rat's gastric mucosa. 130 5


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