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)

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

Copper, through its role as cofactor for lysyl oxidase, is essential for intra- and inter-molecular cross-links in collagen. Copper deficiency, in man and in animals, is associated with bone fragility ascribed to defective cross-links. To assess bone strength in copper-deficient animals, we designed a sensitive torsion-testing apparatus according to biomechanical considerations. Femora from 7 copper-deficient rats and from their pair-fed controls were tested in torsional loading until fracture. Significant decreases in the maximal sustained torque (t = 2.93, p < 0.05), in the ultimate angular deformation (t = 2.52, p < 0.05) and in the toughness (t = 2.88, p < 0.05) were demonstrated. In a complementary study, it was shown that the ash weight and the calcium content of the femora from the copper-deficient animals did not differ from those of the controls. It was likely, therefore, that the impaired mechanical strength was related to defects in the collagen component of bone.
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PMID:Impaired mechanical strength of bone in experimental copper deficiency. 831 18

The typical wound healing process after tooth extraction includes several important biological reactions. The collagen fiber, which is the main organic component of connective tissue, plays an important role in the formation of granulation tissue and also bone tissue. Maturation of collagen is controlled by the intermolecular crosslinks in the collagen fibers. Lysyl oxidase, which catalyzes the corresponding aldehyde formation from certain lysyl and hydroxylysyl residues in collagen and elastin in the first step of the linking reaction, is the only known enzyme required in the crosslinking process. This study was designed to analyze changes in the lysyl oxidase activity and calcium content during the healing of rabbit tooth extraction wounds and to survey the relationship between them. Healing tissue in the extraction sockets was removed 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, and 56 days postoperatively. After decalcification, lysyl oxidase was extracted from wound tissue, and activity of this enzyme was examined by tritium-release assay. Radiographs and histologic sections were also obtained in each group. The results show that lysyl oxidase activity can be detected on the first day postoperatively and that it increases sharply from days five to seven, reaching the peak value on the seventh day. After that, enzyme activity decreases gradually and returns to normal range on day 14. Histologically, the healing sockets were filled mainly with young fibrous connective tissue at day seven; osteoid tissue could be found on the lateral wall and fundus of the extraction sockets at the same time. Accompanying the formation of new bone, calcium content increased conspicuously from day 7 to day 14. These results indicate that lysyl oxidase predominantly acts to promote cross-linking of the abundantly synthesized collagen in the early stage of healing of rabbit tooth extraction wounds. When minerals were precipitated at a great rate in the newly-formed bone, lysyl oxidase activity was concurrently decreased.
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PMID:Changes in lysyl oxidase activity and calcium content during the healing of tooth extraction wounds. 926 Apr 63

Maximum collagen synthesis and maximum accumulation of insoluble collagen occur at different phenotypic stages in developing osteoblastic cell cultures. Insoluble collagen accumulation depends in part on the activity of extracellular enzymes including procollagen N-proteinases, procollagen C-proteinase (derived from the BMP1 gene), and lysyl oxidase. In addition to its action on procollagen, procollagen C-proteinase processes prolysyl oxidase to mature 32-kDa lysyl oxidase. The regulation of extracellular activities that control insoluble collagen accumulation has not been studied extensively. The present study compares molecular events that control production of a collagenous mineralized extracellular matrix in vitro among five different murine osteosarcoma cell clones derived from the same tumor, but which differ in their ability to produce an insoluble mineralized matrix. Levels of insoluble type I collagen, insoluble calcium, bone morphogenetic protein 1 (BMP-1), and lysyl oxidase expression, lysyl oxidase biosynthesis, lysyl oxidase activity, and prolysyl oxidase processing activity were determined. Results surprisingly indicate that lysyl oxidase activity is not related closely to lysyl oxidase messenger RNA (mRNA) levels among the different cell clones. However, it appears that BMP-1-dependent prolysyl oxidase processing could contribute to the observed lysyl oxidase activity. Highest collagen and BMP-1 mRNA levels, prolysyl oxidase processing activity, and lysyl oxidase activity occurred in a cell clone (K8) that showed the highest levels of insoluble collagen accumulation. Culture media from a cell clone (K37) that accumulates little insoluble collagen or calcium but expresses high levels of lysyl oxidase mRNA contained low molecular weight fragments of lysyl oxidase protein and showed low lysyl oxidase activity. By contrast the K14 cell line exhibits relatively high lysyl oxidase activity and collagen accumulation, but low levels of mature lysyl oxidase protein. Together, these studies indicate that catabolic as well as anabolic activities are important in regulating insoluble collagen accumulation in osteoblastic cells. In addition, results suggest that products of genes homologous to lysyl oxidase may contribute to observed lysyl oxidase activity.
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PMID:Molecular events that contribute to lysyl oxidase enzyme activity and insoluble collagen accumulation in osteosarcoma cell clones. 1084 Nov 88

This study aimed at the determination of the influence of exercise on the levels of a number of bone morphogenic enzymes in subchondral bone and at the comparison of these data with other (subchondral) bone-related parameters that have been investigated in the same experimental population.Forty-three foals were reared until weaning at 5 months of age under similar conditions, except for the type and amount of exercise. Fifteen foals remained at pasture (Pasture group and also control group), 14 foals were kept in box stalls (Box group) and 14 foals were kept in the same box stalls but were subjected daily to an increasing number of gallop sprints (Training group). After weaning 8 foals from each group were euthanised. All remaining 19 animals were housed together in a loose box with access to a small paddock to study a possible reversibility of exercise-induced effects. Post mortem subchondral bone samples were collected from the femoropatellar joint and analysed for the bone morphogenic enzymes alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP) and lysyl oxidase (LO). Data were compared to calcium content, numbers of collagen cross-links, bone mineral density (BMD) and cross-sectional area (CSA) collected in other bone-related studies in the same group of experimental animals. At 5 months of age, ALP levels were significantly lower and TRAP levels higher in both the Box and the Training group, making the ALP : TRAP ratio reversed in relation to the Pasture group. LO levels were lower in the Box group only. The ALP and TRAP data corresponded with changes in CSA, but not with calcium and BMD, the levels of which were the same in the Training and Pasture groups. The LO levels corresponded nicely with hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) cross-links. At 11 months of age ALP and TRAP levels had reached similar levels in most groups, normalising the ALP : TRAP ratio. TRAP levels in the former Training group lagged somewhat behind. LO levels were still significantly lower in the former Box rest group. It is concluded that the overall increase in bone mass (characterised by the change in CSA) is apparently related to continuous, evenly distributed exercise as in the Pasture group (natural situation). This process seems to be related with ALP and TRAP levels and their ratio. For normal cross-link levels and BMD, short heavy bouts of exercise superimposed on a basic rest regimen seem sufficient. However, both data from this study and from earlier studies suggest that this latter exercise regimen might have a long-term deleterious effect.
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PMID:The influence of exercise on bone morphogenic enzyme activity of immature equine subchondral bone. 1245 29

Vascular calcification is a common feature of advanced atherosclerosis resulting in reduced elasticity of elastic arteries. However, the relationship between elastic fibers and vascular calcification at the molecular and cellular levels remains unknown. We investigated the expression of major elastic fiber components such as tropoelastin (TE) and fibrillin-1 (FBN1) and elastin-related enzyme, lysyl oxidase (LO), in a calcification model using beta-glycerophosphate (beta-GP) in cultured bovine aortic smooth muscle cells (BASMCs). Ten mM of beta-GP stimulated calcium deposition in a time-dependent manner. As determined by Western blot analysis, 10 mM of beta-GP time-dependently decreased TE and FBN1 protein levels. TE, FBN1, and LO mRNA levels, assessed by reverse transcription-polymerase chain reaction, were also decreased by exposure to 10 mM beta-GP. Furthermore, we investigated whether the processes of calcification in BASMCs directly control these regulations. In experiments using levamisole, an alkaline phosphatase inhibitor, and DMDP, a bisphosphonate, both inhibitors inhibited down-regulation during beta-GP-induced calcification, suggesting that the down-regulation of TE, FBN1, and LO directly relates to calcium deposition. In cases of vascular calcification, the decreased expression of TE, FBN1, and LO may be partially responsible for decreased vascular elasticity and also for the decreased formation of new elastic fibers.
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PMID:Accelerated calcification represses the expression of elastic fiber components and lysyl oxidase in cultured bovine aortic smooth muscle cells. 1256 May 90

Low-intensity pulsed ultrasound (LIPUS) has distinct effects on biologic mineralization at intensities of <100 mW/cm2. Intensity-dependent differences in the pattern of accelerated mineralization may be due to different alterations in regulation of collagenous matrix formation. However, little is known about the influence of LIPUS on collagen metabolism in the context of mineralization processes. Therefore, we attempted to evaluate differential effects of two intensities of pulsed ultrasound (30 vs. 120 mW/cm2) on collagen post-translational modification and mineralization in osteoblastic MC3T3-E1 cells. Murine osteoblastic MC3T3-E1 cells were exposed to pulsed ultrasound (1.5-MHz, 200-ms burst sine wave at 1.0-kHz frequency, either 30 or 120 mW/cm2 SATA, for 20 min/day from Day 14 to Day 35 postconfluence). Expression patterns of lysyl oxidase (LO), procollagen-lysine, 2-oxyglutarate, 5-dioxigenase 1 (PLOD1, LH1), and 2 (PLOD2, LH2) was examined using quantitative PCR. Quantitative analysis of reducible immature cross-links (dihydroxylysinonorleucine, hydroxylysinonorleucine, and lysinonorleucine) and nonreducible mature cross-links (pyridinoline and deoxypyridinoline) as well as analysis of the maturation of immature to mature cross-links were performed. Exposure to 30 mW/cm2 LIPUS upregulated LH2 mRNA expression and enzyme activity compared to controls. It was associated with increased relative amounts of telopeptidyl hydroxylysine (Hyl)-derived cross-links beginning on Day 14, upregulated LO mRNA expression, increased total reducible and nonreducible cross-links, and increased ratios of newly formed nonreducible to reducible cross-links. Similarities in the pattern of cross-link formation and calcium deposition in matrices between 30 mW/cm2 LIPUS-treated MC3T3-E1 cultures and bone suggest that 30 mW/cm2 LIPUS may promote the maturation of collagenous matrix as a scaffold for calcification. In contrast, exposure to 120 mW/cm2 ultrasound increased calcium accumulation compared to control at Day 35, but increases were delayed until Day 25. No differences in the extent and pattern of cross-links were observed compared to controls. These results suggest that the promotion of mineralization induced by 120 mW/cm2 may be attributed to other factors involved in mineralization process rather than cross-link pattern. Our results demonstrated the existence of differential effects of lower versus higher intensities of ultrasound on mineralization processes in vitro.
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PMID:Intensity-related differences in collagen post-translational modification in MC3T3-E1 osteoblasts after exposure to low- and high-intensity pulsed ultrasound. 1533

Atherosclerosis is characterized by inflammatory metabolic change with lipid accumulation in the artery. Atherosclerotic plaque occurs at discrete locations in the arterial system and involves the proliferation of smooth muscle cells (SMCs) together with imbalance of the extracellular matrix elements, elastic fiber in particular. The role of elastin in arterial development and disease was confirmed by generating mice that lack elastin. Thus, elastin is a critical regulatory molecule that regulates the phenotypic modulation, proliferation and migration of SMCs. We estimated that elastin expression and SMC proliferation are coupled inversely: potent stimulators of cell proliferation may potentially inhibit elastin expression and potent inhibitors of cell proliferation can stimulate elastin expression. Moreover, elastin was found to be expressed maximally at the G(0) and minimally at the G(2)/M phase during the cell cycle, suggesting that its expression is regulated by the cell growth state. The elastin peptide VPGVG enhanced SMC proliferation, resulting in the reduction of elastin expression. The inhibition of elastin expression by elastin fragments may be reflected in the negative feedback regulatory mechanism. The relationship between cell proliferation and elastin expression may be changed in atherosclerosis. Areas of atherosclerotic plaque show abnormality of elasticity and permeability from the viewpoint of the physiological function of the arterial wall. The etiology was estimated to be that cholesterol and calcium are deposited on the elastic fiber, resulting in decreased elastin synthesis and cross-linking formation. In addition, these dysfunctions of elastin fiber are also associated, in that the down-regulation of elastin and its related components (fibrillin-1 and lysyl oxidase) are directly related to calcification in SMCs. The denatured arterial elastin by cholesterol and calcium accumulation was also susceptible to proteolytic enzymes such as elastase and matrix metalloproteinase (MMP). Therefore, metabolic change in elastic fiber induces decreased elasticity and is associated with essential hypertension. Vitamin K(2) is used in drug therapy against atherosclerosis, or calcification in diabetes mellitus or dialysis, due to its promotion of the carboxylation of the matrix Gla protein.
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PMID:Atherosclerosis and matrix dystrophy. 1555 5

We have characterized comprehensive transcript and proteomic profiles of cell lines corresponding to normal breast (MCF10A), noninvasive breast cancer (MCF7) and invasive breast cancer (MDA-MB-231). The transcript profiles were first analysed by a modified protocol for representational difference analysis (RDA) of cDNAs between MCF7 and MDA-MB-231 cells. The majority of genes identified by RDA showed nearly complete concordance with microarray results, and also led to the identification of some differentially expressed genes such as lysyl oxidase, copper transporter ATP7A, EphB6, RUNX2 and a variant of RUNX2. The altered transcripts identified by microarray analysis were involved in cell-cell or cell-matrix interaction, Rho signaling, calcium homeostasis and copper-binding/sensitive activities. A set of nine genes that included GPCR11, cadherin 11, annexin A1, vimentin, lactate dehydrogenase B (upregulated in MDA-MB-231) and GREB1, S100A8, amyloid beta precursor protein, claudin 3 and cadherin 1 (downregulated in MDA-MB-231) were sufficient to distinguish MDA-MB-231 from MCF7 cells. The downregulation of a set of transcripts for proteins involved in cell-cell interaction indicated these transcripts as potential markers for invasiveness that can be detected by methylation-specific PCR. The proteomic profiles indicated altered abundance of fewer proteins as compared to transcript profiles. Antisense knockdown of selected transcripts led to inhibition of cell proliferation that was accompanied by altered proteomic profiles. The proteomic profiles of antisense transfectants suggest the involvement of peptidyl-prolyl isomerase, Raf kinase inhibitor and 80 kDa protein kinase C substrate in mediating the inhibition of cell proliferation.
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PMID:Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics. 1631 37

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.
Clin Calcium 2006 Dec
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


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