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)

Morphologic and biochemical analyses were performed to compare normal skin and mature scars to hypertrophic scar and keloid. Correlation of morphologic findings with biochemical profiles of the skin and scar samples proved feasible and enlightening. Scanning electron microscopy (SEM) was used to characterize the architectural arrangement of collagen fibers in skin and scars. Cultured fibroblasts from each specimen were also examined with the SEM. A biochemical profile of each tissue specimen was constructed, characterizing the collagen component of the specimen by sequential molecular sieve and ion exchange chromatography to determine a) the degree of intermolecular crosslinking, b) amino acid analysis, and c) levels of lysyl oxidase activity. Results indicate that collagen fibers and fiber bundles display a decreasing level of organization as the clinical degree of scar abnormality increases, and this structural gradient correlates with the gradient of intermolecular crosslinking in the same tissue--normal skin and mature scar being highly crosslinked, hypertrophic and keloid successively less so. Surprisingly, the level of the crosslinking enzyme lysyl oxidase is normal or elevated in hypertrophic scar and keloid despite the relative lack of crosslinking. Amino acid content was uniform for all specimens. Scanning electron microscopy examination of cultured fibroblasts from the tissue specimens demonstrated three phenotypically distinctive fibroblasts whose numerical and volumetric proportions correlated with the tissue of origin.
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PMID:Pathologic scar formation. Morphologic and biochemical correlates. 1 61

D-Pencillamine is believed to inhibit collagen cross-link biosynthesis by forming thiazolidine rings with lysyl-derived aldehydes that are intermediates in bifunctional cross-link synthesis. Recently, we showed that aldehyde biosynthesis catalyzed by lysyl oxidase occurs after the onset of fibril formation and that nascent aldehydes form Schiff-base cross-links rapidly in fibrils. This suggested that the accessibility of D-penicillamine to most aldehydes formed during cross-link synthesis might be limited. To study this, reconstituted chick bone collagen fibrils were incubated in vitro with highly purified lysyl oxidase and D-penicillamine. As reported in previous studies in vivo, allysine content increased and polyfunctional cross-link synthesis decreased with D-penicillamine. However, the concentration of bifunctional cross-links increased rather than decreased due to a 2-fold increase in N6:6'-dehydro-5,5'-dihydroxylysinonorleucine. Hydroxyallysine, an intermediate in formation of this Schiff base, decreased. A time study indicated that allysine levels increased primarily after the bulk of Schiff base synthesis. These results indicate that D-penicillamine does not inhibit bifunctional cross-link synthesis as previously suggested. Its principal effect is to block synthesis of polyfunctional cross-link products from Schiff base cross-link precursors and to cause accumulation of these precursors. This effect may be due to interference with the close molecular packing required for polyfunctional cross-link synthesis. These results also suggest a mechanism for the relative insensitivity of tissues such as bone with high hydroxylysine content to D-penicillamine. In this study, D-penicillamine caused selective accumulation of allysyl and not hydroxyallysyl residues. In bone as opposed to soft tissues, hydroxyallysyl residues are intermediates in synthesis of almost all cross-links.
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PMID:Collagen cross-linking. Effect of D-penicillamine on cross-linking in vitro. 1 66

Inbred mice bearing certain alleles at the Mottled locus have defects in connective tissue which result in weakness of skin and of blood vessels. Previous studies have established that cross-links in collagen and elastin are decreased in these animals due to impaired formation of lysine-derived aldehydes. Lysyl oxidase activity in extracts of skin is markedly lower in those prepared from affected animals than control mice. An inhibitor of lysyl oxidase is present in equal amounts in affected and control skins and does not account for diminished activity found in affected animals.
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PMID:Decreased lysyl oxidase activity in the aneurysm-prone, mottled mouse. 1 40

Lysyl oxidase had been purified to near homogeneity from bovine aorta and bovine ligamentum nuchae employing a modification of methods described by Harris et al., and Stassen and his colleagues. The aortic enzyme gives rise to at least three peaks and the ligament enzyme resolves into at least four peaks upon chromatography on DEAE cellulose. The molecular weight of each peak of both enzymes is approximately 30,000 daltons in sodium dodecyl sulfate. The aortic enzyme aggregates to species with molecular weights varying from approximately 60,000 to 1,000,000 daltons upon dialysis out of urea into phosphate-buffered saline. Temperature studies reveal that lysyl oxidase is stable to temperatures as high as 80 degrees C, although the assay optimum is 52 degrees C. Studies in progress suggest the temperature dependency of assay may reflect conformational changes in the elastin substrate.
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PMID:Studies on lysyl oxidase of bovine ligamentum nuchae and bovine aorta. 1 72

At 24 h after injection of 16-day chick embryos with [C-3H]pyridoxine hydrochloride, some of this label appears in the epiphysial cartilage. Over 35% of this radioactivity appears in the form of [G-3H]pyridoxal and a further 30% as other vitamin B-6 compounds. Partial purification of lysyl oxidase from the labelled epiphysial cartilage reveals a single peak of radioactivity coinciding with a single peak of enzyme activity. On dialysis against phosphate-buffered saline, 75% of this radioactivity is found to be non-diffusible. After incubation with isonicotinic acid hydrazide, a carbonyl reagent that appears to inhibit lysyl oxidase both in vivo and in vitro, a further 70% of the radioactivity is lost, with a roughly corresponding loss of enzyme activity. It is suggested that a form of vitamin B-6 is required as a cofactor of lysyl oxidase, and that this may have important implications in terms of connective-tissue metabolism.
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PMID:Evidence for the role of vitamin C-6 as a cofactor of lysyl oxidase. 2 11

The activity of lysyl oxidase which catalyzes the initial step of cross-linking of collagen and elastin polypeptides was measured in blood vessels of the hypertensive rat. The enzyme activity was increased in the aorta and mesenteric artery when hypertension was induced in 8-week-old rats with administration of deoxycorticosterone acetate (DOCA) and 1% saline. Reserpine diminished this increase in vascular lysyl oxidase activity concomitant with reduction in blood pressure. When beta-aminopropionitrile, a specific inhibitor of lysyl oxidase, was administered before the onset of DOCA-salt hypertension, the aortic collagen content was reduced markedly. Concomitant with reduction in the aortic collagen content, the development of hypertension and arteriosclerotic changes in the kidney was partially prevented. These results would indicate that hypertension increases the amount and the degree of cross-linking of vascular collagen and that the deposition of excess collagen in the vascular wall contributes to the development of hypertension and arteriosclerosis.
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PMID:Increased lysyl oxidase activity in blood vessels of hypertensive rats and effect of beta-aminopropionitrile on arteriosclerosis. 2 27

Lysyl oxidase catalyzes the crosslinking of collagen and elastin. Lysyl oxidase activity was measured and localized in rat liver during the evolution of hepatic fibrosis induced by CCl4. Enzyme activity measured with DL-[6-3H]-lysine-labeled collagen substrates in liver and plasma increased sharply after approximately 3 wk of injection, reached a maximum at 6 wk, and then decreased. The increase in activity correlated histologically with early connective tissue septa formation, and the magnitude of increase was significantly greater than that found for the intracellular collagen biosynthetic enzymes protocollagen prolyl hydroxylase and lysyl hydroxylase. Indirect immunofluorescence studies showed that lysyl oxidase was present in association with collagen in the extracellular space. However, it was not possible to correlate the distribution pattern with a particular liver cell type. These observations suggest that serial measurements of lysyl oxidase activity in liver or plasma may be useful for correlating changes in connective tissue formation with histologic connective tissue deposition.
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PMID:Biochemical and immunochemical study of lysyl oxidase in experimental hepatic fibrosis in the rat. 2 18

Dermal collagen solubility and lysyl oxidase activity of bones were measured in DDD mice of advancing age. Insoluble fractions of the dermal collagen increased more rapidly in females than in males after 5 weeks of age. Activity of the lysyl oxidase extracted from bones was higher in females than in males after 4 weeks of age. After sexual maturation, such sex differences were always observed in skin as well as in bone tissue. In other experimental animals, dermal collagen solubility was markedly decreased by estrogen treatment and lysyl oxidase was remarkably activated by estrogen in both skin and bone. Thus it is clear that estrogen stimulates the enzyme activity and accelerates the maturation of collagen and elastin in extracellular space.
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PMID:Changes in collagen cross-linking and lysyl oxidase by estrogen. 2 34

Defective copper metabolism was demonstrated in male mice bearing the blotchy (Moblo/y) allele at the mottled locus on the X-chromosome. Copper absorption from the gut was only 64% of that found in normal mice and hepatic copper levels were only 56% of the controls. Ceruloplasmin and heart cytochrome c oxidase activities were normal, yet lysyl oxidase activity from cultured fibroblasts was only 45% of control levels. Copper accumulated in fibroblasts cultured from these mutants to values that were five times normal. The accumulation of copper in the fibroblasts was associated with a protein of approximately 12,000 molecular weight.
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PMID:Abnormal cellular copper metabolism in the blotchy mouse. 2 91

The formation of isodesmosine and desmosine in vitro by the action of lysyl oxidase on tropoelastin was studied. The synthesis of desmosines occurred in the absence of additional substances. The formation of desmosines was not affected by removal of molecular O2 from the reaction medium nor was it affected by the lack of proline hydroxylation in tropoelastin. However, there was virtually no desmosine formation at 15 degrees C, a temperature not conducive to coacervation, indicating that coacervation is an important prerequisite for cross-linking.
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PMID:Elastin cross-linking in vitro. Studies on factors influencing the formation of desmosines by lysyl oxidase action on tropoelastin. 3 Apr 49


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