Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.4.3.13 (lysyl oxidase)
1,248 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inspiration of CdCl2 results in a focally fibrotic response in rat lungs and markedly increases the activity of lung lysyl oxidase. Western blot analyses of urea-extractable rat lung proteins revealed that the levels of an immunoreactive, 32,000-Da protein were markedly increased in the cadmium-exposed rat lung tissue, consistent with the induction of lysyl oxidase protein. Anion exchange chromatography revealed low levels of multiple peaks of catalytically functional lysyl oxidase in control rat lung extracts, while the profile of cadmium-exposed rat lung extracts displayed markedly elevated levels of multiple peaks of enzyme activity indicating that the charge heterogeneity is expressed in the activated enzyme. The cadmium-induced enzyme was purified as a species of 32 kDa, without resolving individual ionic variants. The catalytic and physical properties of the isolated enzyme were very similar to those of previously well characterized basal enzyme of bovine aorta, including the presence of a pyrroloquinoline quinone-like carbonyl cofactor. The copper and cadmium content of the cadmium-induced enzyme indicated little if any replacement of tightly-bound copper by cadmium in the exposed lung.
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PMID:Induction of lung lysyl oxidase activity and lysyl oxidase protein by exposure of rats to cadmium chloride: properties of the induced enzyme. 167 59

Effects of cadmium (Cd) on lysyl oxidase activity and copper (Cu) metabolism in bone were studied using Cu-deficient rats supplemented with Cu and/or Cd in a diet. When fed for 8 weeks on a diet containing 0.3 ppm or less Cu (-Cu diet), weanling rats revealed anemia, and markedly decreased plasma ceruloplasmin activity and serum Cu to less than 15% of normal level, showing features of Cu-deficiency. These rats were divided into four groups and refed for another 2 weeks on the following diets: Group I, -Cu diet; Group II, -Cu diet with 50 ppm Cd (+Cd diet); Group III, -Cu diet supplemented with 15 ppm Cu (+Cu diet); group IV, -Cu diet with both Cu and Cd (+Cu/+Cd diet). After 2 weeks, serum Cu levels of Groups I, II, III and IV were 1.8, 0.8, 78 and 74% of the normal control level (1.438 +/- 0.060 micrograms/ml), respectively. Concentrations of Cu in epi- and metaphyses of the control group, Groups I, II, III and IV were 1.45 +/- 0.20, 0.67 +/- 0.08, 0.76 +/- 0.12, 1.40 +/- 0.31 and 1.22 +/- 0.05 micrograms/g wet tissue, in that order. Concentrations of Cd in epi- and metaphysis increased in only Groups II and IV and were 0.15 +/- 0.03 and 0.18 +/- 0.01 micrograms/g wet tissue, respectively. Thus, having both Cd and Cu supplements in a diet did not inhibit each other's uptake into the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of dietary cadmium and/or copper on the bone lysyl oxidase in copper-deficient rats relative to the metabolism of copper in the bone. 197 55

The spectral and catalytic properties of the copper cofactor in highly purified bovine aortic lysyl oxidase have been examined. As isolated, various preparations of purified lysyl oxidase are associated with 5-9 loosely bound copper atoms per molecule of enzyme which are removed by dialysis against EDTA. The enzyme also contains 0.99 +/- 0.10 g atom of tightly bound copper per 32-kDa monomer which is not removed by this treatment. The copper-free apoenzyme, prepared by dialysis of lysyl oxidase against alpha,alpha'-dipyridyl in 6 M urea, catalyzed neither the oxidative turnover of amine substrates nor the anaerobic production of aldehyde at levels stoichiometric with enzyme active site content, thus contrasting with the ping pong metalloenzyme. Moreover, the spectrum of the apoenzyme was not measurably perturbed upon anaerobic incubation with n-butylamine, while difference absorption bands were generated at 250 and 308 nm in the spectrum of the metalloenzyme incubated under the same conditions. A difference absorption band also developed at 300-310 nm upon anaerobic incubation of pyrroloquinoline quinone, the putative carbonyl cofactor of lysyl oxidase, with n-butylamine. Full restoration of catalytic activity occurred upon the reconstitution of the apoenzyme with 1 g atom of copper/32-kDa monomer, whereas identical treatment of the apoenzyme with divalent salts of zinc, cobalt, iron, mercury, magnesium, or cadmium failed to restore catalytic activity. The EPR spectrum of copper in lysyl oxidase is typical of the tetragonally distorted, octahedrally coordinated Cu(II) sites observed in other amine oxidases and indicates coordination by at least three nitrogen ligands. The single copper atom in the lysyl oxidase monomer is thus essential at least for the catalytic and possibly for the structural integrity of this protein.
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PMID:Structural and catalytic properties of copper in lysyl oxidase. 197 46

Industrial workers who are accidentally exposed to cadmium fumes often develop severe lung damage leading to widespread peribronchiolar scarring. This study examined the effect of a single exposure of cadmium chloride aerosol on rat lung lysyl oxidase and prolyl hydroxylase, both markers of connective tissue biosynthesis. Rats were killed at 2, 4, 7, 10, and 21 days after a 2-h exposure to 0.1% Cdcl2 aerosol. Total lung lysyl oxidase was increased 14.8 times that a saline control animals by 4 days and returned to near normal values by 10 days. Interestingly, a small amount of lysyl oxidase activity was also detectable in the lung lavage of unexposed animals and was markedly elevated at the earlier times after cadmium exposure. Total lung prolyl hydroxylase activity paralleled that of lung lysyl oxidase and increased 7.4-fold by the fourth day. A significant increase in total lung hydroxyproline could be demonstrated. Administration of beta-aminopropionitrile, an irreversible inhibitor of lysyl oxidase, prevented much of the increase in lysyl oxidase activity and the accumulation of collagen. The altered tissue amounts of lysyl oxidase and prolyl hydroxylase after cadmium inhalation correlated well with the marked interstitial cell hyperplasia 4 to 5 days after exposure and suggested that connective tissue protein synthesis is activated in the interstitial cell fibroblasts soon after cadmium exposure.
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PMID:Lung lysyl oxidase and prolyl hydroxylase: increases induced by cadmium chloride inhalation and the effect of beta-aminopropionitrile in rats. 611 50

Comparisons were made between morphologic and biochemical changes occurring in the lungs of rats receiving a single exposure or repeated 2-h exposures of aerosolized 0.1% cadmium chloride, simulating varied exposure conditions potentially experienced by humans. Lung lysyl oxidase activity increases in both models, although less so with repeated exposures. Pulsing lung tissue in vitro with 3H-proline indicated that rates of collagen biosynthesis were elevated preferentially over rates of noncollagen protein synthesis in both exposure models. Lung metallothionein increased nearly linearly over 21 days of repeated exposure. Histologic examination revealed scarred lesions distorting alveolar structure and bronchioles in both models. However, scarring and cell exudation into the airways and interstitium was less in the repeatedly exposed model. The results indicate the activation of a connective tissue repair reaction in both models. Increased levels of metallothionein after repeated exposure may both sequester cadmium and reduce pools of copper available for lysyl oxidase synthesis, thus limiting the fibrotic response.
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PMID:Alterations in collagen biosynthesis and in metallothionein in lungs of rats acutely or repeatedly exposed to cadmium chloride aerosol. 614 24

The effect of cadmium (Cd) on the solubility of bone collagen was examined in cultured tibiae from 9-day chick embryos. The solubility of collagen was not significantly increased by 8.9 microM Cd, but showed a significant increase at 13.4 microM Cd. As the [3H]hydroxyproline (Hyp) formation was inhibited by Cd at 8.9 and 13.4 microM [3H]Hyp formation and collagen solubility were investigated in the presence of 200 microM Fe2+, a metal which is known to prevent the inhibitory effects of Cd on prolyl hydroxylase in vitro. Fe affected neither a decrease in [3H]Hyp formation nor an increase in collagen solubility caused by Cd. This suggests that a Cd-induced increase in collagen solubility may be due to the decrease of lysyl oxidase activity, not to the formation of underhydroxylated collagen. Zn at 48 and 134 microM depressed the Cd-induced increase in collagen solubility, but caused no increase in collagen solubility. Our present and previous results suggest that Zn can protect the disturbance of both the collagen synthesis and the collagen cross linking caused by Cd.
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PMID:The effect of cadmium on the collagen solubility of embryonic chick bone in tissue culture. 646 37

Hair samples were collected from 74 patients with idiopathic adolescent scoliosis and from 25 control children and were analyzed for content of the following minerals: copper, sodium, iron, zinc, potassium, magnesium, cadmium, calcium, and manganese. The hair copper level of the scoliotic children was significantly higher than that of the controls. The scoliosis mean was 6.5 micrograms/dl and the control mean was 3.6 micrograms/dl, P less than 0.025. There was no correlation between the amount of hair copper and the severity of the scoliosis. The authors suggest that copper may be a factor in the development of scoliosis since it is part of the lysyl oxidase enzymes that are required for cross-linking of collagen and elastin. Another connection is that postpubertal girls have higher copper levels than boys and also have a greater severity of scoliosis.
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PMID:Elevated hair copper level in idiopathic scoliosis: preliminary observations. 739 62

Lysyl oxidase, a copper-dependent metalloenzyme, plays a central role in crosslinking of collagen and elastin in the extracellular matrix. Notably, lung lysyl oxidase activity is markedly stimulated in rats exposed to cadmium vapors. To further understand the mechanism of cadmium toxicity, the mRNA expression, synthesis, post-translational processing, and catalytic activity of lysyl oxidase were examined in cadmium-resistant (CdR) cells and the cadmium-sensitive Swiss mouse 3T3 cells from which they were derived. These CdR cells synthesized and accumulated markedly elevated levels of metallothionein, a known marker for cadmium resistance, whereas the expression of lysyl oxidase was reduced considerably. In comparison to the parental, cadmium-sensitive cells, the suppression of enzyme production in the CdR cells was seen at the mRNA level, at the levels of intracellular proprotein production and mature enzyme secreted into the medium, and in terms of total enzyme activity in the culture. The presence of cupric chloride in the culture medium during the incubation of the CdR cells for 16 h significantly enhanced lysyl oxidase activity accumulating in the medium, suggesting that lysyl oxidase deficiency in CdR cells may be related to abnormal copper metabolism.
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PMID:Downregulation of lysyl oxidase in cadmium-resistant fibroblasts. 754 71

The moose (Alces alces L.) in an acid rain affected region in south-west Sweden has developed a complex disease with numerous clinical signs, most of which are consistent with those of secondary copper (Cu) deficiency and/or molybdenosis in cattle and sheep. The clinical signs of the moose disease reported to date include diarrhoea, anorexia, emaciation, achromotrichia, alopecia, sudden heart failure and osteoporosis. Findings at necropsy included mucosal oedema, atrophied lymphoid tissues of the mucous membranes of the alimentary tract, neuropathy, neuronal degeneration and uni- or bilateral corneal opacity. In a study of clinically healthy animals from the affected region in Sweden over a 12-year period (1982-1994), the hepatic Cu concentration decreased by 50% and the liver and kidney cadmium (Cd) concentration decreased by 25-35%, while the molybdenum (Mo) concentration increased by 20-40%. These changes are probably related to an increase in the pH of the soil and water in the moose environment and a consequent change in the uptake of these elements by the plants consumed by the moose. It is noteworthy that the occurrence of the disease in the mid 1980s coincided with increased liming undertaken to counteract the noxious effects of acid rain in this region. Clinical signs and lesions of the moose disease resemble those reported for Cu deficiency and/or molybdenosis in cattle and sheep. To elucidate the complex, multi-faceted clinical signs of the moose disease, the clinical signs and necropsy findings are discussed in relation to the biochemical functions of certain well-known Cu-dependent enzymes, e.g. depigmentation of hair due to depressed tyrosinase activity, osteoporosis by depressed lysyl oxidase activity, sudden heart failure due to decreased activity of lysyl oxidase, cytochrome c oxidase and Cu/Zn-superoxide dismutase; in addition, mucosal lesions and ulcerations due to loss of activity of diamine oxidase as well as of lysyl oxidase and cytochrome c oxidase. It is concluded from the present findings that the moose disease is most probably a Cu deficiency and/or a molybdenosis-type syndrome.
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PMID:'Mysterious' moose disease in Sweden. Similarities to copper deficiency and/or molybdenosis in cattle and sheep. Biochemical background of clinical signs and organ lesions. 949 61

Copper (Cu)-dependent lysyl oxidase (LO) catalyzes crosslinking of collagen and elastin stabilizing the extracellular matrix (ECM). Chronic inhalation of cadmium (Cd), a toxic metal, induces emphysema. To probe mechanisms of Cd injury to the lung, we developed Cd-resistant (CdR) cells from rat fetal lung fibroblasts (RFL6) by chronic exposure to CdCl(2) from 1 to 40 microM and further examined their expressions of LO, LO substrates, and Cu-scavenging thiols. Levels of cellular thiols, metallothionein, and glutathione in CdR cells were elevated to 13.0- and 3.2-fold of parental controls, respectively, whereas LO mRNA and protein levels were markedly reduced in these cells, with catalytic activity declining to only 16% of the parental control. A conspicuous 52 kDa species rather then the normal 50 kDa proenzyme appeared in the CdR cell extract but not in the conditioned medium, which was codistributed with the endoplasmic reticulum marker [DiOC5(3)] within the cell, implying the Cd-induced 52 kDa species as a product of an abnormal LO-processing defect in secretion. Addition of Cu into CdR cell cultures enhanced the expression of LO mRNA, protein and catalytic activities reflecting limitation of Cu bioavailability for LO in these cells. With inhibition of LO, CdR cells also displayed downregulation of collagen and elastin, substrates of LO. Restoration of collagen synthesis by exposure of CdR cells to purified LO or Cu suggests that inhibition of LO and limitation of Cu cofactor by Cd, as key phenotype changes, accelerated collagen and elastin damage, a critical event pertinent to emphysema pathogenesis.
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PMID:Inhibition of the expression of lysyl oxidase and its substrates in cadmium-resistant rat fetal lung fibroblasts. 1643 78


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