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)

Diabetes mellitus is associated with a number of changes in the cornea. These include increased corneal autofluorescence, thickening and enhanced endothelial cell permeability. In this study we have investigated the biochemical changes of corneal collagen due to advanced Maillard reaction and lysyl oxidase mediated crosslinking in diabetes. Advanced Maillard reaction was estimated by collagen-bound fluorescence and pentosidine. Hydroxypyridinium (a trifunctional fluorescent crosslink) was estimated as an index of lysyl oxidase mediated crosslinking. Both fluorescence (p < 0.05) and pentosidine were present at higher levels in diabetic corneas when compared with age-matched control corneas. Hydroxypyridinium levels were only marginally increased in diabetes. These results suggest that corneal collagen is modified in diabetes by advanced Maillard reaction and that such modifications may have effect on corneal thickening, endothelial cell permeability and other abnormalities of the cornea in diabetes.
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PMID:Advanced Maillard reaction and crosslinking of corneal collagen in diabetes. 757 46

Alterations in the integrity of the extracellular matrix play an important role in osteoarthritis. Matrix crosslinks in articular cartilage of the knee were studied in partially meniscectomized rabbits to compare changes due to osteoarthritis with those occurring during aging. Pyridinoline, a lysyl oxidase-initiated crosslink, and pentosidine, a crosslink formed by the Maillard/glycation reaction, were assayed separately on reverse-phase high performance liquid chromatography. A significant increase in the percentage of insoluble collagen was observed in normal 12-month-old rabbits compared with the levels in 3-month-old animals, whereas osteoarthritis was associated with a shift toward more soluble fractions. Total pyridinoline content did not change with age or osteoarthritis. Total pentosidine, however, increased significantly with age but remained constant with osteoarthritis. Analysis of the distribution of crosslinks among solubility fractions indicated a significant shift of pyridinoline from the pepsin-released fraction to the insoluble fraction with osteoarthritis, but no changes were observed with age. Pentosidine distribution shifted toward the pepsin-released fraction in osteoarthritis, with a shift toward the insoluble fraction with age. Because of the low levels of pentosidine present, its precise location, whether collagenous or noncollagenous, remains unclear. However, since pentosidine represents a marker for the overall Maillard reaction, the results of our studies support a role for Maillard reaction products in the aging of extracellular matrix. The shift of pentosidine toward more soluble fractions suggests the presence of matrix degradation and repair in osteoarthritis.
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PMID:Lysyl oxidase and Maillard reaction-mediated crosslinks in aging and osteoarthritic rabbit cartilage. 785 94

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

Based on the present definition of osteoporosis, both bone density and quality are important factors in the determination of bone strength. Collagen crosslinking is a determinant of bone quality. Cross-links can form enzymatically by the action of lysyl oxidase or non-enzymatically, resulting in advanced glycation end products. Collagen crosslinking is affected by tissue maturation as well as the degree of mineralization. Homocysteine and vitamin B6 (pyridoxal) are also regulatory factors of collagen crosslinking. We elucidate the relationship between the degree of mineralization and collagen cross-links in cancellous bone from hip fracture cases. We also determined plasma levels of homocysteine and pyridoxal. Twenty-five female intracapsular hip fracture cases (78 +/- 6 years) and 25 age-matched postmortem controls (77 +/- 6 years) were included in this study. Collagen crosslinking was analyzed after each bone specimen was fractionated into low (1.7-2.0 g/ml) and high (>2.0 g/ml) density fractions. The content of enzymatic (immature reducible and mature nonreducible cross-links) and nonenzymatic cross-link (pentosidine) were determined. In the controls, there was no difference in total enzymatic cross-links between low and high density bone, while pentosidine content was significantly higher in high density bone. In the fracture cases, not only reduced enzymatic cross-links in high density bone and increased pentosidine in both low and high density bone, but also higher plasma homocysteine and lower pyridoxal levels were evident compared with the controls. These results indicate that detrimental crosslinking in both low and high mineralized bone result in impaired bone quality in osteoporotic patients.
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PMID:Degree of mineralization-related collagen crosslinking in the femoral neck cancellous bone in cases of hip fracture and controls. 1696 91

Impaired bone quality has been proposed as a cause of increased bone fragility in osteoporosis. Collagen crosslinking is a candidate for determining the material properties of bone. Collagen cross-links are of two types; lysyl oxidase (LOX) and lysyl hydroxylase (PLOD1; LH1, PLOD2; LH2b) controlled cross-links, and advanced glycation end products, pentosidine. Homocysteine and vitamin B(6) (pyridoxal) are also regulatory factors of collagen crosslinking. Recently, we reported that in the femoral neck fracture cases, not only reduced enzymatic cross-links in old osteon and increased pentosidine in both young and old osteons from cortical and cancellous bone, but also higher plasma homocysteine and lower pyridoxal levels were evident compared with the controls (Osteoporos Int 2006. Calcif Tissue Int, 2006). In this review, we describe that mildly hyperhomocysteinemia, and vitamin B(6) or vitamin D insufficiency are crucial determinants of detrimental crosslinking of bone collagen in patients with hip fracture.
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PMID:[Elevated plasma concentration of homocysteine, low level of vitamin B6, pyridoxal, and vitamin D insufficiency in patients with hip fracture: a possible explanation for detrimental cross-link pattern in bone collagen]. 1714 27

Bone quality is thought to encompass the structural and material properties of bone that are affected by turnover rate. The concept of bone quality is included in Japanese Guideline for Osteoporosis prevention and treatment. Evidence has accumulated that collagen cross-links play important roles in bone strength. We have demonstrated that the quantitative and qualitative deterioration of lysyl oxidase controlled and non-enzymatic cross-links (Advanced glycation end products, AGEs, Pentosidine) of collagen in patients with osteoporotic femoral neck fracture cases might be affected by hyperhomocysteinemia (Saito M, Calcif Tissue Int, 2006), oxidative stress, vitamin B status (Saito M, Osteoporos Int, 2006) . Recently, Shiraki et al. demonstrated that a functional polymorphism in methylenetetrahydrofolate reductase (MTHFR) polymorphism, T allele (C677T), may be a risk factor for future fracture in addition to the traditional risk factors (Shiraki M, Saito M, et al., J Bone Miner Metab, in press). In addition, we have reported that a higher urinary pentosidine was an independent risk factor, for vertebral fracture in a 5-year prospective study in Japanese women (Shiraki M, Saito M, et al., J Bone Miner Metab, 2008). If confirmed in large, prospective trials, measurement of serum homocysteine and serum or urinary excretion of pentosidine might be characterized as markers reflecting bone collagen deterioration.
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PMID:[Daily practice using the guidelines for prevention and treatment of osteoporosis. How do we realize the bone quality in routine practice using Japanese guideline for osteoporosis prevention and treatment?]. 1867 47

The primary functional role of collagen is as a supporting tissue and it is now established that the aggregated forms of the collagen monomers are stabilised to provide mechanical strength by a series of intermolecular cross-links. In order to understand the mechanical properties of collagen, it is necessary to identify and quantitatively determine the concentration of the cross-links during their changes with maturation, ageing and disease. These cross-links are formed by oxidative deamination of the epsilon-amino group of the single lysine or hydroxylysine in the amino and carboxy telopeptides of collagen by lysyl oxidase, the aldehyde formed reacting with a specific lysine or hydroxylysine in the triple helix. The divalent Schiff base and keto-amine bonds so formed link the molecules head to tail and spontaneously convert during maturation to trivalent cross-links, a histidine derivative and cyclic pyridinolines and pyrroles, respectively. These latter bonds are believed to be transverse inter-fibrillar cross-links, and are tissue rather than species specific. We describe the determination of these cross-links in detail.Elastin is also stabilised by cross-linking based on oxidative deamination of most of its lysine residues to yield tetravalent cross-links, desmosine and iso-desmosine, the determination of which is also described.A second cross-linking pathway occurs during ageing (and to a greater extent in diabetes mellitus) involving reaction with tissue glucose. The initial product glucitol-lysine can be determined as furosine and pyridosine, and determination of advanced glycation end-products believed to be cross-links, such as pentosidine, are also described.
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PMID:quantitative determination of collagen cross-links. 1924 1

Collagen cross-links play important roles in the expression of bone strength and the proper biological function of bone. The cross-links of collagen can be roughly divided into two types : lysyl oxidase mediated cross-links (enzymatic immature and mature cross-links) and advanced glycation end-products (AGEs ; nonenzymatic cross-links, pentosidine) . Recently, we show that reduction in enzymatic cross-links and excessive formation of nonenzymatic crossl-links, pentosidine in bone could be important for explaining the variation of fracture susceptibility in osteoporosis (Osteoporos Int 17 (7) : 986-995, 2006) and diabetes (Osteoporos Int 17 (10) : 1514-1523, 2006) . We also demonstrate that urinary excretion AGEs cross-link, pentosidine is a novel risk for future vertebral fracture (J Bone Miner Metab 26 (1) : 93-100, 2008) . Such deteriorated cross-links in osteoporosis may be induced by moderately elevated homocysteine in sera (Osteoporos Int 2009 in press, Calcif Tissue Int 79 (3) : 160-168, 2006, J Bone Miner Metab 26 (6) : 595-602, 2008) . These results indicate that elevated serum or urine pentosidine and plasma homocysteine levels in osteoporosis and diabetes is useful marker for estimation of fracture risk independent of bone turnover and bone mineral density. In this review, I summarize the recent literatures regarding bone quality markers.
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PMID:[Biochemical markers of bone turnover. New aspect. Bone collagen metabolism: new biological markers for estimation of bone quality]. 1963 94

Bone quality is thought to encompass the structural and material properties of bone that are affected by the turnover rate. Evidence has accumulated that collagen cross-links play important roles in bone strength. We have demonstrated that the quantitative and qualitative deterioration of lysyl oxidase control and non enzymatic cross-links (advanced glycation end products, AGEs, pentosidine) of collagen in patients with osteoporotic femoral neck fracture might be affected by hyperhomocysteinemia, oxidative stress, and vitamin B6 insufficiency. Recently, Shiraki et al. demonstrated that a functional polymorphism in methylenetetrahydrofolate reductase (MTHFR) polymorphism, T allele (C677T), may be a risk factor for future fracture in addition to the traditional risk factors. Further, we reported that a higher urinary pentosidine level was an independent risk factor for vertebral fracture in a 5-year prospective study involving Japanese women. If confirmed in large, prospective trials, measurements of serum homocysteine and serum or urine levels of pentosidine might be characterized as markers reflecting bone collagen deterioration.
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PMID:[Bone quality markers: pentosidine, homocysteine, and MTHFR polymorphism]. 1986 Feb 14

Evidence has accumulated that collagen cross-links also play important roles in bone strength and the proper biological functions of bone. Thus, collagen cross-links may be a factor in determining the material properties of bone. Collagen cross-linking is affected by some growth factors, and tissue age. Collagen cross-links can be roughly divided into two types : lysyl oxidase mediated cross-links (enzymatic immature, divalent and mature, trivalent cross-links) and advanced glycation end-products (AGE ; non-enzymatic, pentosidine cross-links). These two types vary by both the mechanism of formation and by functional differences. Hyper- and micro-gravity, weight-bearing, and low intensity pulsed ultrasound (LIPUS) have distinct biological effects on bone collagen cross-link formation in vitro and in vivo (Saito M, J Bone Miner Res 2003, Bone 2004, Calcif Tissue Int 2004) . We demonstrated in previous studies that physiologic levels of mechanical strain such as hypergravity, weight-bearing, and LIPUS induce the formation of bone-type collagenous matrix into a specific molecular packing arrangement through the formation of characteristic types of cross-links as mineralization begins. Collagen cross-links play important roles in the expression of bone strength and the proper biological function of bone. Thus, collagen cross-links are thought to be a determinant of bone quality. While LIPUS have beneficial effects on collagen enzymatic cross-link formation, mechanical stress may improve bone quality (Saito M, Osteoporos Int, REVIEW, 2010) .
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PMID:[Musculoskeletal rehabilitation and bone. Mechanical stress and bone quality : do mechanical stimuli alter collagen cross-link formation in bone? "Yes" ]. 2035 25


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