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)

A total of 160 1-2 day old chickens were fed a 2% cholesterol diet for a period of 8 to 42 days and compared with an equal number of controls. Aortas were analyzed for various indexes of reactivity of connective tissue, cholesterol content and scanning electron microscopy (SEM) characteristics of the endothelial lining. Cholesterol feeding for a period up to 6 weeks resulted in doubling the level of serum cholesterol. It was, however, without effect on the activity of prolyl hydroxylase, lysyl oxidase, collagenase and collagen content in the aortic wall. As early as 3 weeks of feeding significant changes occurred in total and esterified cholesterol content. At the same time endothelial cells were characteristically contracted with several long cytoplasmic elongations and protrusions. A significant decrease of activity of the above enzymes was found in aortic tissue with increased age of the chicken. Collagen content in aortas increased with age of chickens. It is concluded that cholesterol as an atherogenic agent induces marked changes in endothelial cells and lipids of chicken aorta at earlier periods, prior to the activation of connective tissue.
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PMID:Early changes in the arterial wall of chickens fed a cholesterol diet. 0 48

The lung of the tight-skin (TSK) mouse was characterized by enlargement of the air spaces. Elastin in the alveolar walls of the TSK mouse exhibited fragmentation. The aorta of the TSK mouse was characterized by marked hyperplasia of loose connective tissue in the adventitia. Collagen fibres and ruthenium red-positive materials were markedly increased. Microfibrils surrounding elastin in the adventitia of the aorta were not clear in the TSK mouse. In the lung of the beta-aminopropionitrile (BAPN)-fed mouse, enlargement of the alveolar air spaces was not prominent compared with the TSK mouse. Elastic fibres in the alveolar walls did not show the fragmentation observed in the TSK mouse, and microfibrils surrounding elastin were clearly observed. However, elastic laminae in the media of the BAPN-fed mouse aorta were swollen and fragmented. Elastic fibres in the adventitia exhibited a normal appearance and microfibrils surrounding elastin in the adventitia were clearly observed. The results suggest that the mechanism of the connective tissue abnormality in the TSK mouse is different from that of BAPN, which inhibits the activity of lysyl oxidase. The abnormality of elastin and microfibrils surrounding elastin in the TSK mouse probably plays a role in the deformity or degradation of elastic fibres and the structural changes of the lung.
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PMID:Electron microscopic observations of elastic fibres in the lung and aorta of tight-skin and beta-aminopropionitrile-fed mice. 157 33

Considerable progress has been made in our understanding of nonenzymatic glycation of collagen, and the relationship between glycation of collagen and changes in connective tissue associated with aging and diabetes. Recent studies surveyed in this review suggest the following conclusions: 1. Collagen content of early glycation products does not appear to increase throughout the life span in normal human subjects, although small increases may occur that are linked to glycemic changes. These products are increased, relative to age-matched controls, in experimental diabetes and in diabetes mellitus in collagen from virtually all tissues analyzed. 2. Collagen content of browning products increases with aging and appears to be higher in diabetic subjects than in age-matched controls. Rates of accumulation may be accelerated in subpopulations of diabetic subjects at high risk for developing complications. 3. Increases in early glycation products do not appear to be associated with alterations in collagen solubility, thermal rupture time, or mechanical strength, nor is there an association with most diabetic complications. Alterations in these products may, however, affect conformation, ligand binding, lysyl oxidase-mediated cross-linking, and interactions between collagen and other macromolecules in the extracellular matrix. 4. Increased content of browning products is associated with many physicochemical changes in collagen as well as with long-term complications in diabetes mellitus. 5. Regulatory mechanisms have been identified in vivo that may serve to control or limit the formation of glycation products. 7. Pharmacologic agents have been identified that may be able to reduce collagen content of late glycation products. Despite the progress that has been made in this field, many areas of uncertainty and controversy exist. For example, there is not yet a consensus that the browning products associated with collagen exclusively comprise advanced Maillard products derived from nonenzymatically glycated residues. There is evidence that oxidative reactions involving lipids also play a role in generating fluorophores and chromophores that may alter properties of collagen. Thus, in the extracellular matrix collagen may be continuously modified by at least three very different processes: Maillard reactions, interactions with oxidizing lipids, and enzymatically mediated cross-linking. The interrelationships between these and possibly other posttranslational modifications remain a poorly understood area of great complexity.
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PMID:Nonenzymatic glycation of collagen in aging and diabetes. 198 39

Collagen composition and cross-linking in human keloid and normal skin tissues were analyzed biochemically. CNBr peptides were separated by 2-dimensional (2-D) mapping and high performance liquid chromatography (HPLC). The amounts of type I and type III collagen was quantified by 2-D scanning densitometry of fluorographs of 2-D maps derived from samples radioactively labelled in vitro by [3H]-NaBH4 in dimethylformamide. Keloid tissues contained 31.6 +/- 2.2 percent type III collagen as compared to 21.4 +/- 2.7 percent type III present in normal human skin dermis. HPLC profiles of CNBr peptides showed that approximately 5 percent of the high molecular weight material in keloids is mercaptoethanol reducible, compared to insignificant amounts in normal skin. 2-D maps derived from CNBr peptides of keloid collagen demonstrated thiol reduction sensitive alpha 1(III)-CB9 dimer as well as 24,000- and 32,000-dalton CNBr peptides, which were not mercaptoethanol reduction sensitive in normal skin due to cross-linking via the lysyl oxidase pathway. Also, a group of 20,000- to 25,000-dalton CNBr peptides, in the alpha 1(I)-CB6 cross-linking region were prominent in keloid tissues.
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PMID:Alteration of collagen composition and cross-linking in keloid tissues. 221 57

Collagen fibers in the ovarian follicle undergo drastic changes at ovulation due to the preovulatory increase of collagenolytic activities. The collagen synthesis in ovaries, however, has not been elucidated yet. To clarify the regulatory role of prostaglandins (PGs) in collagen synthesis of the follicular wall in relation to the ovulatory process, we measured prolyl hydroxylase (PH), as well as lysyl oxidase (LO) activity and the content of hydroxyproline (Hyp) in ovarian follicles of the rabbits treated by hCG, hCG/indomethacin (IM) and hCG/IM/various PGs. The experimental groups consisted of; 1) untreat control group 2) ovulatory group receiving hCG 3) non-ovulatory group given PGs 4) ovulatory group given hCG and PGs 5) group in which hCG-induced ovulation was inhibited by IM (4 mg/kg) 6) group in which IM-inhibited ovulation was recovered by PGF2 alpha (1.5 mg/kg) 7) group in which IM-inhibited ovulation was not restored by PGE1 (0.1 mg/kg) and PGE2 (0.7 mg/kg). The peak activities of PH and LO in ovarian follicles were observed at 12-13 hr after hCG injection, namely, immediately after ovulation. Significant changes of these activities after hCG administration were specific to the ovaries. PH activity in the ovaries was suppressed by the administration of IM, but LO activity was not significantly suppressed. In the hCG/IM/PGF2 alpha-treated ovulatory rabbits (Group 6), PH activity recovered to nearly the level of the hCG-treated rabbits (Group 2). By addition of PGE2, ovulation did not recover but PH activity was restored to about 70% of the hCG-treated rabbits. PGE1 did not have any effect on the reversal of ovulation-blockage or restoration of PH activity. The amount of Hyp after hCG administration tended to decrease from 6 hr to 10 hr but was significantly increased from 10 hr to 13 hr. This increase of Hyp after ovulation significantly correlated with the increase of PH and LO activities. In the hCG/IM/PGF2 alpha-treated rabbits (Group 6), the changes of Hyp were similar to those the hCG-treated rabbits (Group 2). In conclusion, collagen synthetic activity, found to be regulated by PH and LO activities in the ovarian follicles, was activated after follicle rupture, resulting in reconstruction of collagen fibers, and PGs play an important role in the ovulatory process by modifying collagen synthesis.
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PMID:[Effect of prostaglandins on collagen synthesis in rabbit ovarian follicles during the ovulatory process]. 287 49

Collagen analysis of articular cartilage and subchondral bone was performed on femoral heads obtained from patients of late stage of aseptic necrosis (ANF) (4 cases), and osteoarthritis (OA) (7 cases). In articular cartilage of both diseases, there was not observed any difference in the solubility of collagen compared with normal articular cartilage. However, collagen contents determined by hydroxyproline analysis showed a decrease in both diseases; this tendency was prominent in OA. On the other hand, copper contents showed an increase in ANF while there was a decrease in OA; the fact may suggest that lysyl oxidase acts actively on the formation of a precursor of cross-links in collagen matrix of articular cartilage in ANF. In subchondral bone of both diseases, collagen contents showed an increase in OA, and a decrease in ANF compared with normal subchondral bone. However the solubility of collagen has increased in both diseases. Moreover, lysine hydroxylation and copper contents showed an increase in both OA and ANF; these findings suggest that repairing reaction of the pathological lesion by proliferation of undifferentiated tissue remained even in late stage of the disease. In this paper, the author also discussed about the connective tissue metabolism of these two diseases by determination the types of collagen molecules of pathological cartilage and bone.
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PMID:[Experimental study on the development of aseptic necrosis of femoral head--with comparison of osteoarthritis of the hip in collagen metabolism]. 405 23

We studied several members of a family with an X-linked form of cutis laxa; the affected males have mild skin laxity, a characteristic facies, skeletal abnormalities, structural abnormalities of the genitourinary tract, and low serum copper levels. The activity of lysyl oxidase, a copper-dependent enzyme involved in cross-link formation in collagen, was decreased in skin-biopsy specimens (13 to 26 per cent of normal) and in culture medium from cells to two affected males (15 to 20 per cent of normal). Immunoreactive lysyl oxidase from skin of both patients was virtually undetectable by immunodiffusion assay. The amounts of lysyl-derived aldehydes (the product formed in collagen and elastin by lysyl oxidase) and of cross-links formed from these products were decreased in dermal fibroblasts in culture. Collagen extractability from these cells was increased in culture. These findings suggest that lysyl oxidase deficiency provides the biochemical basis of the X-linked form of cutis laxa.
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PMID:X-linked cutis laxa: defective cross-link formation in collagen due to decreased lysyl oxidase activity. 610 92

Glucose inhibits collagen fibril formation in vitro. A linear dose response was observed, with half-maximum inhibition of fibril formation occurring at 50 mM glucose. Nonfibrillar collagen cannot be cross-linked by lysyl oxidase, an enzyme that catalyzes the initial cross-linking reaction. The degree of decreased fibril formation correlated with the loss of ability of the collagen to serve as a substrate for lysyl oxidase. Collagen that is not cross-linked is unstable and more susceptible to collagenolytic attack. Interference with collagen cross-linking and more rapid degradation may explain the decreased amounts of interstitial collagen and the poor healing of wounds associated with diabetes mellitus.
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PMID:Inhibition of collagen fibril formation in vitro and subsequent cross-linking by glucose. 614 99

This study was designed to investigate the effects of lifetime diet restriction on collagen crosslinking in skin, tail tendon, aorta, and lung in mice. Difunctional enzymatic crosslinks decreased with age in all tissues except skin, while mature crosslinks showed almost no change with age. Collagen-associated fluorescence, assayed in skin and tail tendon, increased with age, as did pentosidine, a specific advanced glycation product, in aorta. There was no change in glucitolyllysine content with age. Difunctional crosslinks, glucitolyllysine, and collagen-associated fluorescence were decreased in diet-restricted animals relative to ad libitum fed animals in some tissues at some time points; however, correlations were not observed among these different effects, or between different tissues. Diet restriction did not affect nonreducible "mature" crosslinks. These studies suggest that: (1) lifetime diet restriction is associated with decreased collagen-associated fluorescence, suggestive of advanced glycation products, in older animals; (2) age-related increases in collagen stiffening and its decrease by dietary restriction cannot be explained solely by alterations in lysyl oxidase-mediated crosslinking, the levels of which are tissue dependent; (3) lysyl oxidase-mediated crosslinking and nonenzymatic glycation of collagen are independently influenced by dietary restriction and aging.
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PMID:Influence of age and long-term dietary restriction on enzymatically mediated crosslinks and nonenzymatic glycation of collagen in mice. 812 49

Cultured osteoblasts from chick embryo calvaria were used as a model system to investigate the post-translational extracellular mechanisms controlling the macroassembly of collagen fibrils. The results of these studies demonstrated that cultured osteoblasts secreted a collagenous extracellular matrix that assembled and mineralized in a defined temporal and spatial sequence. The assembly of collagen occurred in a polarized fashion, such that successive orthogonal arrays of fibrils formed between successive cell layers proceeding from the culture surface toward the media. Mineralization followed in the same manner, being observed first in the deepest and oldest fibril layers. Collagen fibrillogenesis, the kinetics of cross-link formation, and collagen stability in the extracellular matrix of the cultures were examined over a 30 day culture period. Between days 8 and 12 in culture, collagen fibril diameters increased from < 30 nm to an average of 30-45 nm. Thereafter, diameters ranged in size from 20 to 200 nm. Quantitation of the collagen cross-linking residues, hydroxylysyl pyridinoline (HP) and lysyl pyridinoline (LP), showed that these mature cross-links increased from undetectable levels to concentrations found in normal chick bone. Analysis of the kinetics of their formation by pulse-chase labeling the cultures with [3H]lysine showed a doubling time of approximately 5 days. The relationships between cross-link formation, fibrillogenesis, and collagen stability were examined in cultures treated with beta-aminopropionitrile (beta-APN), a potent inhibitor of lysyl oxidase and cross-link formation. In beta-APN-treated cultures, total collagen synthesis was increased twofold, with no change in mRNA levels for type I collagen, whereas the amount of collagen accumulated in the cell layer was decreased by 50% and mineral deposition was reduced. The rate of collagen retention in the matrix was assessed by pulse-chase analysis of [3H]proline over a 16 day period in control and beta-APN-treated cultures. In control cultures, about 20% of the labeled collagen was lost from the cell layers over a 16 day period compared with > 80% in the presence of beta-APN. The beta-APN-treated cultures also showed a wider diversity of fibril diameters with a median in the > 45-60 nm range. In summary, these data suggest that cross-linking and assembly of collagen fibrils secreted by osteoblasts in vitro occur in a fashion similar to that found in vivo. The rate of cross-link formation is relatively constant and may be correlated with increasing collagen mass.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Post-translational control of collagen fibrillogenesis in mineralizing cultures of chick osteoblasts. 823 72


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