scholarly journals Native cross-links in collagen fibrils induce resistance to human synovial collagenase

1979 ◽  
Vol 181 (3) ◽  
pp. 639-645 ◽  
Author(s):  
C A Vater ◽  
E D Harris ◽  
R C Siegel
Keyword(s):  
Lysyl Oxidase ◽  
Collagen Fibrils ◽  
Bone Collagen ◽  
Collagen Molecule ◽  
Cross Linking ◽  
Pathological Conditions ◽  
Insoluble Material ◽  
Induce Resistance ◽  
Cross Links

A model system consisting of highly purified lysyl oxidase and reconstituted lathyritic chick bone collagen fibrils was used to study the effect of collagen cross-linking on collagen degradation by mammalian collagenase. The results indicate that synthesis of approx. 0.1 Schiff-base cross-link per collagen molecule results in a 2–3-fold resistance to human synovial collagenase when compared with un-cross-linked controls or samples incubated in the presence of beta-aminopropionitrile to inhibit cross-linking. These results confirm previous studies utilizing artificially cross-linked collagens, or collagens isolated as insoluble material after cross-linking in vivo, and suggest that increased resistance to collagenase may be one of the earliest effects of cross-linking in vivo. The extent of intermolecular cross-linking among collagen fibrils may provide a mechanism for regulating the rate of collagen catabolism relative to synthesis in normal and pathological conditions.

scholarly journals Collagen cross-linking. Isolation of cross-linked peptides from collagen of chicken bone

1973 ◽  
Vol 135 (3) ◽  
pp. 393-403 ◽  
Author(s):  
D. R. Eyre ◽  
M. J. Glimcher
Keyword(s):  
Amino Acid ◽  
Bone Collagen ◽  
Collagen Molecule ◽  
Cross Linking ◽  
Bacterial Collagenase ◽  
Chicken Bone ◽  
Cross Links ◽  
The Cross ◽  
Significant Pathway ◽  
Carboxy Terminal

Cross-linked peptides were isolated from chicken bone collagen that had been digested with CNBr or with bacterial collagenase. Analyses of 3H radioactivity in disc electrophoretic profiles of the CNBr peptides from bone collagens that had been treated with NaB3H indicated that a major site of intermolecular cross-linking in chicken bone collagen is located between the carboxy-terminal region of an α1 chain and a small CNBr peptide, probably situated near the amino-terminus of an α1 or α2 chain in an adjacent collagen molecule. A small amount of this cross-linked CNBr peptide was isolated from a CNBr digest of chicken bone collagen by column chromatography. Amino acid analysis showed that the CNBr peptide, α1CB6B, the carboxy-terminal peptide of the α1 chain, was the major CNBr peptide in the preparation, and the reduced cross-linking components were identified as hydroxylysinohydroxynorleucine (HylOHNle), with a smaller amount of hydroxylysinonorleucine (HylNle). However, the composition and the low recovery of the cross-linking amino acids suggested that the preparation was a mixture of CNBr peptides α1CB6B and α1CB6B cross-linked to a small CNBr peptide whose identity could not be determined. A small cross-linked peptide was isolated from chicken bone collagen that had been reduced with NaB3H4 and digested with bacterial collagenase. This peptide was the major cross-linked peptide in the digest and contained a stoicheiometric amount of the reduced cross-linking compounds. A peptide which had the same amino acid composition, but contained the cross-linking compounds in their reducible forms, was isolated from a collagenase digest of chicken bone collagen that had not been treated with NaBH4. The absence of the reduced cross-links from this peptide indicates that, at least for the cross-linking site from which the peptide derives, natural reduction is not a significant pathway for biosynthesis of stable cross-links. However, most of the reducible cross-linking component in the peptide appeared to stabilize in the bone collagen by rearrangement from aldimine to ketoamine form.

Lysyl oxidases: from enzyme activity to extracellular matrix cross-links

2019 ◽  
Vol 63 (3) ◽  
pp. 349-364 ◽  
Author(s):  
Sylvain D. Vallet ◽  
Sylvie Ricard-Blum
Keyword(s):  
Extracellular Matrix ◽  
Molecular Mechanisms ◽  
Catalytic Domain ◽  
Lysyl Oxidase ◽  
Dimensional Structure ◽  
Cross Linking ◽  
Copper Binding ◽  
Molecular Features ◽  
Ecm Proteins ◽  
Cross Links

Abstract The lysyl oxidase family comprises five members in mammals, lysyl oxidase (LOX) and four lysyl oxidase like proteins (LOXL1-4). They are copper amine oxidases with a highly conserved catalytic domain, a lysine tyrosylquinone cofactor, and a conserved copper-binding site. They catalyze the first step of the covalent cross-linking of the extracellular matrix (ECM) proteins collagens and elastin, which contribute to ECM stiffness and mechanical properties. The role of LOX and LOXL2 in fibrosis, tumorigenesis, and metastasis, including changes in their expression level and their regulation of cell signaling pathways, have been extensively reviewed, and both enzymes have been identified as therapeutic targets. We review here the molecular features and three-dimensional structure/models of LOX and LOXLs, their role in ECM cross-linking, and the regulation of their cross-linking activity by ECM proteins, proteoglycans, and by inhibitors. We also make an overview of the major ECM cross-links, because they are the ultimate molecular readouts of LOX/LOXL activity in tissues. The recent 3D model of LOX, which recapitulates its known structural and biochemical features, will be useful to decipher the molecular mechanisms of LOX interaction with its various substrates, and to design substrate-specific inhibitors, which are potential antifibrotic and antitumor drugs.

scholarly journals Cross-linking modifications of HDL apoproteins by oxidized phospholipids: structural characterization, in vivo detection, and functional implications

2020 ◽  
Vol 295 (7) ◽  
pp. 1973-1984
Author(s):  
Detao Gao ◽  
Mohammad Z. Ashraf ◽  
Lifang Zhang ◽  
Niladri Kar ◽  
Tatiana V. Byzova ◽  
...  
Keyword(s):  
Density Lipoprotein ◽  
Cross Linking ◽  
Oxidized Phospholipids ◽  
Cross Link ◽  
In Vivo Detection ◽  
Lysine Residues ◽  
Cross Links ◽  
Human Atheroma

Apolipoprotein A-I (apoA-I) is cross-linked and dysfunctional in human atheroma. Although multiple mechanisms of apoA-I cross-linking have been demonstrated in vitro, the in vivo mechanisms of cross-linking are not well-established. We have recently demonstrated the highly selective and efficient modification of high-density lipoprotein (HDL) apoproteins by endogenous oxidized phospholipids (oxPLs), including γ-ketoalkenal phospholipids. In the current study, we report that γ-ketoalkenal phospholipids effectively cross-link apoproteins in HDL. We further demonstrate that cross-linking impairs the cholesterol efflux mediated by apoA-I or HDL3 in vitro and in vivo. Using LC-MS/MS analysis, we analyzed the pattern of apoprotein cross-linking in isolated human HDL either by synthetic γ-ketoalkenal phospholipids or by oxPLs generated during HDL oxidation in plasma by the physiologically relevant MPO-H2O2-NO2− system. We found that five histidine residues in helices 5–8 of apoA-I are preferably cross-linked by oxPLs, forming stable pyrrole adducts with lysine residues in the helices 3–4 of another apoA-I or in the central domain of apoA-II. We also identified cross-links of apoA-I and apoA-II with two minor HDL apoproteins, apoA-IV and apoE. We detected a similar pattern of apoprotein cross-linking in oxidized murine HDL. We further detected oxPL cross-link adducts of HDL apoproteins in plasma and aorta of hyperlipidemic LDLR−/− mice, including cross-link adducts of apoA-I His-165–apoA-I Lys-93, apoA-I His-154–apoA-I Lys-105, apoA-I His-154–apoA-IV Lys-149, and apoA-II Lys-30–apoE His-227. These findings suggest an important mechanism that contributes to the loss of HDL's atheroprotective function in vivo.

scholarly journals A new glycation product ‘norpronyl-lysine,’ and direct characterization of cross linking and other glycation adducts: NMR of model compounds and collagen

2014 ◽  
Vol 34 (2) ◽  
Author(s):  
Peter T. B. Bullock ◽  
David G. Reid ◽  
W. Ying Chow ◽  
Wendy P. W. Lau ◽  
Melinda J. Duer
Keyword(s):  
Model Systems ◽  
Cross Linking ◽  
Advanced Glycation ◽  
Model Compounds ◽  
Product Characterization ◽  
Glycation Product ◽  
Cross Links

NMR reveals numerous early and advanced glycation products, including a newly recognized ‘norpronyl-lysine,’ and cross links in solution, intact collagen and model systems. Solid state methods are directly applicable to in vitro and in vivo glycation pathway and product characterization.

scholarly journals Characterization of Genipin-Modified Dentin Collagen

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hiroko Nagaoka ◽  
Hideaki Nagaoka ◽  
Ricardo Walter ◽  
Lee W. Boushell ◽  
Patricia A. Miguez ◽  
...  
Keyword(s):  
Amino Acid ◽  
Lysyl Oxidase ◽  
Biomechanical Properties ◽  
Biochemical Properties ◽  
Cross Linking ◽  
Dependent Manner ◽  
Cross Link ◽  
Concentration Dependent Manner ◽  
Cross Links ◽  
Dentin Collagen

Application of biomodification techniques to dentin can improve its biochemical and biomechanical properties. Several collagen cross-linking agents have been reported to strengthen the mechanical properties of dentin. However, the characteristics of collagen that has undergone agent-induced biomodification are not well understood. The objective of this study was to analyze the effects of a natural cross-linking agent, genipin (GE), on dentin discoloration, collagen stability, and changes in amino acid composition and lysyl oxidase mediated natural collagen cross-links. Dentin collagen obtained from extracted bovine teeth was treated with three different concentrations of GE (0.01%, 0.1%, and 0.5%) for several treatment times (0–24 h). Changes in biochemical properties of NaB3H4-reduced collagen were characterized by amino acid and cross-link analyses. The treatment of dentin collagen with GE resulted in a concentration- and time-dependent pigmentation and stability against bacterial collagenase. The lysyl oxidase-mediated trivalent mature cross-link, pyridinoline, showed no difference among all groups while the major divalent immature cross-link, dehydro-dihydroxylysinonorleucine/its ketoamine in collagen treated with 0.5% GE for 24 h, significantly decreased compared to control (P< 0.05). The newly formed GE-induced cross-links most likely involve lysine and hydroxylysine residues of collagen in a concentration-dependent manner. Some of these cross-links appear to be reducible and stabilized with NaB3H4.

scholarly journals The influence of 1-hydroxyethane-1,1-diphosphonate and dichloromethanediphosphonate on lysine hydroxylation and cross-link formation in rat bone, cartilage and skin collagen

1981 ◽  
Vol 196 (1) ◽  
pp. 303-310 ◽  
Author(s):  
H L Guenther ◽  
H E Guenther ◽  
H Fleisch
Keyword(s):  
Condensation Product ◽  
Bone Collagen ◽  
Cross Link ◽  
Skin Collagen ◽  
Cross Links ◽  
The Cross ◽  
Lysine Hydroxylation ◽  
And Cartilage ◽  
Rat Bone

The effects in vivo of dichloromethanediphosphonate and 1-hydroxyethane 1,1-diphosphonate on collagen solubility, hydroxylation of lysine and proline and on the formation of collagen intermolecular cross-links were studied by using rat bone, cartilage and skin tissues. Dichloromethanediphosphonate decreased bone collagen solubility both in acetic acid and after pepsin treatment. Although none of the diphosphonates had any effect on the hydroxylation of proline, dichloromethane-diphosphonate, but not 1-hydroxyethane-1,1-diphosphonate, increased the number of hydroxylysine residues in the alpha-chains of bone, skin and cartilage collagen. The stimulatory effect was dose-dependent. The dichloromethanediphosphonate-mediated increase in hydroxylysine residues in bone and cartilage was manifested in an increase of dihydroxylysinonorleucine, the cross-link that is formed by the condensation of two hydroxylysine residues. The cross-link hydroxylysinonorleucine, a condensation product of hydroxylysine and lysine, on the other hand, was decreased. The total number of intermolecular cross-links was not changed by the diphosphonate.

scholarly journals Non-equilibrium growth and twist of cross-linked collagen fibrils

Soft Matter ◽  
2021 ◽  
Author(s):  
Matthew P. Leighton ◽  
Laurent Kreplak ◽  
Andrew D. Rutenberg
Keyword(s):  
Collagen Fibril ◽  
Fibril Formation ◽  
Collagen Fibrils ◽  
Size Exclusion ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Fibril Structure ◽  
Cross Links ◽  
Equilibrium Growth

Motivated by evidence for size-exclusion of the enzyme responsible for catalyzing cross-links during in vivo collagen fibril formation, we present a nonequilibrium coarse-grained model for fibril structure and radius control.

scholarly journals Peptidoglycan synthesis in Bacillus licheniformis. The inhibition of cross-linking by benzylpenicillin and cephaloridine in vivo accompanied by the formation of soluble peptidoglycan

1975 ◽  
Vol 146 (1) ◽  
pp. 253-267 ◽  
Author(s):  
Z Tynecka ◽  
J B Ward
Keyword(s):  
Cell Wall ◽  
Bacillus Licheniformis ◽  
Cross Linking ◽  
Cross Links ◽  
Increased Sensitivity ◽  
Cross Bridges ◽  
Chain Lengths ◽  
Soluble Material ◽  
Subsequent Addition

The synthesis of peptidoglycan by an autolysin-deficient β-lactamase-negative mutant of Bacillus licheniformis was studied in vivo in the absence of protein synthesis. Benzylpenicillin and cephaloridine inhibited the formation of cross-bridges between newly synthesized peptidoglycan and the pre-existing cell wall. This inhibition, detected by measurement of the incorporation of N-acetyl[14C]glucosamine into the glycan fraction of the cell wall, was reversed by treatment with β-lactamase and washing. Inhibition of D-alanine carboxypeptidase by benzylpenicillin was not reversed under similar conditions. Cells in which the initial penicillin inhibition of transpeptidation had been reversed showed an increased sensitivity to a subsequent addition of the antibiotic. Chemical analysis of peptidoglycan synthesized after reversal of penicillin inhibition revealed the presence of excess of alanine resulting from the continued inhibition of D-alanine carboxypeptidase. When the cell walls were digested to yield muropeptides so that the degree of cross-linking could be measured, the product after reversal of penicillin inhibition contained fewer cross-links than did the control preparation. Cultures treated with benzylpenicillin and cephaloridine continued to synthesize uncross-linked soluble peptidoglycan, which accumulated in the medium. This soluble material was all newly synthesized peptidoglycan and did not result from autolysis of the bacteria. The average chain lengths of the glycan synthesized in vivo and released as soluble peptidoglycan in the presence of both benzylpenicillin and cephaloridine were similar to those found previously in this organism.

scholarly journals Cross-linking of membrane immunoglobulin D, in the absence of T cell help, kills mature B cells in vivo.

1995 ◽  
Vol 181 (2) ◽  
pp. 515-525 ◽  
Author(s):  
F D Finkelman ◽  
J M Holmes ◽  
O I Dukhanina ◽  
S C Morris
Keyword(s):  
Cell Death ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Number ◽  
Cross Linking ◽  
Membrane Immunoglobulin ◽  
Cross Links ◽  
T Cell Help

In vivo experiments were performed to determine whether the cross-linking of membrane immunoglobulin (mIg) D on mature B cells, in the absence of T cell help, leads to B cell death. Mice were injected with either a monoclonal antibody (mAb) that cross-links mIgD effectively or a mAb that binds to mIgD avidly but cross-links it to a limited extent, and effects on B cell number and B cell Ia, mIgM, and mIgD expression were observed. In most experiments, mice were pretreated with anti-interleukin 7 mAb to prevent the generation of new bone marrow B cells, and with anti-CD4 mAb to prevent the generation of T cell help. In some experiments, mice also received anti-Fc gamma RII mAb to prevent cross-linking of mIgD with Fc gamma RII, and cobra venom factor to prevent possible mIg-complement receptor interactions and complement-mediated killing of B cells. The results of these studies demonstrate that (a) even limited cross-linking of mIgD on mature B cells can lead to B cell death; (b) increased cross-linking of mIgD leads to increased B cell death; (c) the loss of B cells is first detected 2 d after anti-IgD mAb injection and increases during the subsequent 3 d; (d) sustained modulation of mIgD may be necessary to cause B cell death; (e) mIgMdull but not mIgMbright B cells are lost in mice injected with anti-IgD mAbs; and (f) T cell help prevents or minimizes B cell death.

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