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)

Lysyl oxidase activity was measured in lung extracts of hamsters with elastase-induced emphysema 8 days after administration of the enzyme and again after 2, 3, and 4 wk. Levels of activity rose rapidly to 7 times the base values determined in the lungs of saline-injected control animals. In parallel with the increase in lysyl oxidase activity, the rate of 14C-lysine incorporation into desmosine and isodesmosine was at its maximum 1 wk after elastase administration, reflecting the lysyl-oxidase-mediated cross-link formation, which is the final step in the resynthesis of the pulmonary elastin destroyed by the elastolytic insult.
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PMID:Stimulation of lung lysyl oxidase activity in hamsters with elastase-induced emphysema. 285 74

The nonelastolytic proteases trypsin and chymotrypsin were administered to hamsters 24 hours after intratracheal injection of elastase. Severity of the disease, extent of degradation and resynthesis, new cross-link formation, and the levels of the enzyme lysyl oxidase, which mediates the cross-link formation, were compared with the same parameters measured in hamsters with experimental emphysema induced by elastase alone. Increases in mean linear intercept indicated that a more severe form of the disease was produced. Although elastin degradation after 1 week was similar in both groups, resynthesis of the elastin destroyed by the elastolytic insult was significantly impaired in the animals injected sequentially with elastase and trypsin or chymotrypsin. Formation of new elastin as monitored by 14C-lysine incorporation into the elastin specific cross-links desmosine and isodesmosine was reduced approximately 40%, although there was no significant difference in the levels of lysyl oxidase activity. It is suggested that the most likely mechanism compatible with the recorded observations involves destruction of the microfibrillar component of the elastic fiber by trypsin or chymotrypsin, resulting in the absence of the requisite template for resynthesis of the pulmonary elastin.
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PMID:Impairment of elastin resynthesis in the lungs of hamsters with experimental emphysema induced by sequential administration of elastase and trypsin. 285 57

Lysyl oxidase, the enzyme responsible for mediating crosslink formation in collagen and elastin, requires copper for its activity. In this study, lysyl oxidase activity and insoluble elastin content were unchanged in lungs from copper-deficient hamsters compared to controls. The lack of dramatic diminution in lysyl oxidase activity in animals who demonstrate significant structural alterations in the lung suggests that other mechanisms in addition to inhibition of crosslink formation are operative in this model.
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PMID:Lysyl oxidase activity in lungs of copper-deficient hamsters. 285 44

Extracts of bovine ligamentum nuchae have been assayed for lysyl oxidase activity using as substrates soluble elastin and soluble collagen labeled with tritiated lysine. The assays were performed in the presence and absence of sodium oleate. At 0.8 mM, oleate decreased activity with elastin more than 50% and enhanced activity with collagen to approximately 200% that of controls without oleate. The results show that this hydrophobic anion modulates lysyl oxidase specificity in crude extracts and suggests a mechanism for modifying activity in tissues.
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PMID:Modulation of lysyl oxidase substrate specificity by the oleate anion. 285 98

Weanling and perinatal rats were rendered vitamin B-6 (pyridoxine)-deficient. The rat pups were nursed from vitamin B-6-deficient or -sufficient dams and were killed at day 15 after parturition. The weanling rats were fed vitamin B-6-deficient or -sufficient diets and were killed after 5 weeks of treatment. Lung elastin from the groups of rats was then studied with respect to its content of lysine-derived cross-linking amino acids. Lung lysyl oxidase activity was also measured. B-6 deficiency decreased the number of lysine residues in elastin that were converted into the cross-linking amino acid precursor allysine. However, a more significant defect in cross-link formation was an apparent block in the condensation steps leading to the formation of desmosine. Desmosine was decreased, with an increase in the amounts of aldol condensation products (aldol CP) in elastin. It is proposed that the elevation in aldol CP results from the formation of thiazines, which are produced from the reaction between aldehyde and homocysteine. The concentration of homocysteine is significantly elevated in vitamin B-6-deficient rats.
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PMID:Effect of vitamin B-6 (pyridoxine) deficiency on lung elastin cross-linking in perinatal and weanling rat pups. 286 42

Metal-chelating drugs were employed to investigate the role of copper (Cu) in elastin metabolism during the period of alveolarization in rat lung. Six groups of pregnant Sprague-Dawley rats were fed one of six semipurified diets, i.e., sufficient or deficient in copper, or the same basal diet containing 0.2% or 0.4% D-penicillamine (DPA), or the same basal diet containing 0.2% or 0.4% triethylenetetramine (TETA). The dams were fed throughout gestation, parturition, and lactation. The pups were then killed postnatally at day 10 and day 21 for the various analyses. At day 21, liver copper in the Cu-deficient pups was 3-5% control levels. In drug-treated groups, liver copper was 16-30% control levels. In the 21-day-old Cu-deficient rats, the concentration of lung elastin was only 75% of its concentration in control. Lung lysyl oxidase activity was lower in Cu-deficient rats, and data for the relative distribution of lung elastin cross-linking amino acids indicated impaired cross-linking in the pups from both the Cu-deficient and the 0.4% DPA groups. Morphologic examination of the lung also indicated dilation of airways in these two groups. Data on the distribution of cross-linking amino acids in elastin samples were also consistent with previous suggestions that impaired cross-linking observed in copper deficiency or from DPA treatment results from different mechanisms. Since the intakes of DPA and TETA were chosen to be in the therapeutic range of intakes used to treat diseases of abnormal copper metabolism, an important feature of these studies is that DPA and perhaps TETA have the potential of impairing normal lung development.
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PMID:Elastin metabolism during perinatal lung development in the copper-deficient rat. 286 45

Lung tissue from groups of chicks raised 23 d on diets deficient in copper had a higher proportion of 0.15 M NaCl-extractable collagen but lower aldehyde-reacting compounds and elastin than controls the same age. Although the lungs from deficient chicks weighed less, the ratio of lung to body weight for the two groups stayed relatively constant throughout the 23-d period. Lysyl oxidase activity in lungs of deficient chicks was strongly suppressed. Feeding the deficient chicks the diet with copper supplements restored lysyl oxidase activity in lung. This showed the close and specific control of lung lysyl oxidase by copper. The impairment in cross-linking through lysyl oxidase failure is implied from these studies. Clearly, copper is needed for the normal development of lung.
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PMID:Biochemical defect in chick lung resulting from copper deficiency. 286 81

The connective tissue network in striated muscle, consisting principally of collagen is arranged in a three dimensional network and is intimately associated with muscle function. Previous studies have shown that animals maintained on a copper-deficient diet undergo myocardial hypertrophy and exhibit cardiovascular lesions such as ventricular aneurysms that eventually rupture. A deficiency of copper in the diet is known to inhibit lysyl oxidase, a metalloenzyme requiring copper as a cofactor and which is also responsible for collagen and elastin crosslinking. Examination by scanning and transmission electron microscopy of skeletal and cardiac muscle from rats maintained on copper-deficient diets showed both gross and microscopic lesions to the connective tissue network. Immunohistochemical staining by light microscopy with antibodies against lysyl oxidase showed that the enzyme was equally present in both control and experimental animals. Fluorescent staining for antibodies against collagen types I and III showed similar results. From these studies we concluded that the collagen secreted during hypertrophy was not crosslinked by lysyl oxidase due to the absence of the copper cofactor. This resulted in the failure of the connective tissue network to transmit and distribute the increased force associated with myocardial hypertrophy and resulted in myocardial aneurysms.
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PMID:Alteration of the connective tissue network of striated muscle in copper deficient rats. 286 28

The activity of lysyl oxidase, the cross-linking enzyme of elastin and collagen, was measured in culture media of human skin fibroblasts, human aortic medial smooth muscle cells (SMCs) and adventitial fibroblasts using [3H]lysine-labelled elastin substrate. In addition, biosynthesis of isodesmosine and desmosine, the cross-linking amino acids of elastin, was studied by metabolic labelling with [14C]lysine and subsequent amino acid chromatography of protein hydrolysates. Lysyl oxidase activity in culture media of skin fibroblasts and aortic smooth muscle cells increased with the growth of the cell population and was at the highest level in cultures of high cell density. Lysyl oxidase activity in the aortic cell cultures was about three times that of skin fibroblasts. Aortic smooth muscle cells synthesized at least 100 times more desmosines than skin or adventitial fibroblasts. No differences were observed in lysyl oxidase activity and synthesis of desmosines between aortic smooth muscle cells or skin fibroblasts from patients with the Marfan syndrome or other annulo-aortic ectasia (dilatation of the ascending aorta) and the corresponding controls.
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PMID:Lysyl oxidase activity and synthesis of desmosines in cultured human aortic cells and skin fibroblasts: comparison of cell lines from control subjects and patients with the Marfan syndrome or other annulo-aortic ectasia. 286 71

Previous studies have pointed towards a cofactor role for pyridoxal 5'-phosphate (PLP) in lysyl oxidase, the enzyme that generates the peptidyl aldehyde precursor to the lysine-derived cross-linkages in elastin and collagen. The nature of a carbonyl moiety in purified bovine aortic lysyl oxidase was explored in the present study. A PLP dinitrophenylhydrazone could not be isolated from lysyl oxidase, although corresponding preparations of aspartate aminotransferase, a PLP-dependent enzyme, yielded this derivative, as revealed by h.p.l.c. Analysis of lysyl oxidase for PLP after reduction of the enzyme by NaBH4, a procedure that converts PLP-protein aldimines into stable 5'-phosphopyridoxyl functions, also proved negative in tests using monoclonal antibody specific for this epitope. Lysyl oxidase was competitively inhibited by phenylhydrazine, and inhibition became irreversible with time at 37 degrees C, displaying a first-order inactivation rate constant of 0.4 min-1 and KI of 1 microM. [14C]Phenylhydrazine was covalently incorporated into the enzyme in a manner that was prevented by prior modification of the enzyme with beta-aminopropionitrile, a specific active-site inhibitor, and which correlated with functional active-site content. The chemical stability of the enzyme-bound phenylhydrazine exceeded that expected of linkages between PLP and proteins. The absorption spectrum of the phenylhydrazine derivative of lysyl oxidase was clearly distinct from that of the phenylhydrazone of PLP. It is concluded that lysyl oxidase contains a carbonyl cofactor that is not identical with PLP and that is bound to the enzyme by a stable chemical bond.
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PMID:Reactivity of a functional carbonyl moiety in bovine aortic lysyl oxidase. Evidence against pyridoxal 5'-phosphate. 287 97


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