scholarly journals The chemistry of the collagen cross-links. Age-related changes in the reducible components of intact bovine collagen fibres

1973 ◽  
Vol 131 (4) ◽  
pp. 771-780 ◽  
Author(s):  
Simon P. Robins ◽  
Massami Shimokomaki ◽  
Allen J. Bailey
Keyword(s):  
Schiff Bases ◽  
Analytical Techniques ◽  
Growth Period ◽  
Postnatal Growth ◽  
Cross Link ◽  
Bovine Collagen ◽  
Age Related ◽  
Cross Links ◽  
The One

The change in the amounts of the three major reducible cross-links was followed throughout the bovine-life span. The major reducible cross-link in embryonic skin is 6,7-dehydro-Nε -(2-hydroxy-5-amino-5-carboxypentyl)hydroxylysine, but this is gradually replaced in the latter stages of gestation or early postnatal growth period by two other Schiff bases, 6,7-dehydro-Nε-(5-amino-5-carboxypentyl)hydroxylysine and a component not yet identified, designated Fraction C. These latter two Schiff bases increase in amount during the rapid growth period to a maximum, after which they then slowly decrease until at maturity they are virtually absent. The proportion of these Schiff bases closely reflects the rate of growth, i.e. the amount of newly synthesized collagen present at any one time. Similarly, the three Schiff bases present in tendon and the one in cartilage slowly decrease during maturation. No evidence for the possible stabilization of these aldimine bonds during maturation by reduction in vivo was found by three different analytical techniques. Concurrently with the decrease in the proportion of the Schiff bases some new reducible components increased during maturation, but their characterization as Nε-glycosylamines demonstrated that they were not related to the lysine-derived aldehyde components. The significance of these components in the aging process cannot at present be assessed. As no evidence was obtained for any new reducible cross-links replacing the Schiff bases, it is probable that the latter are intermediate cross-links and that during maturation they are stabilized to some as yet unknown non-reducible cross-link as previously proposed (Bailey, 1968).

scholarly journals Age-related changes in collagen synthesis and degradation in rat tissues. Importance of degradation of newly synthesized collagen in regulating collagen production

1991 ◽  
Vol 276 (2) ◽  
pp. 307-313 ◽  
Author(s):  
P K Mays ◽  
R J McAnulty ◽  
J S Campa ◽  
G J Laurent
Keyword(s):  
Skeletal Muscle ◽  
Collagen Synthesis ◽  
Rat Tissues ◽  
Age Related ◽  
Developmental Growth ◽  
Cross Links ◽  
Fractional Synthesis ◽  
Synthesis And Degradation ◽  
Age Related Changes

During developmental growth, collagens are believed to be continuously deposited into an extracellular matrix which is increasingly stabilized by the formation of covalent cross-links throughout life. However, the age-related changes in rates of synthetic and degradative processes are less well understood. In the present study we measured rates of collagen synthesis in vivo using a flooding dose of unlabelled proline given with [14C]proline and determining production of hydroxy[14C]proline. Degradation of newly synthesized collagen was estimated from the amount of free hydroxy [14C]proline in tissues 30 min after injection. Collagen fractional synthesis rates ranged from about 5%/day in skeletal muscle to 20%/day in hearts of rats aged 1 month. At 15 months of age, collagen fractional synthesis rates had decreased markedly in lung and skin, but in skeletal muscle and heart, rates were unchanged. At 24 months of age, synthesis rates had decreased by at least 10-fold in all tissues, compared with rates at 1 month. The proportion of newly synthesized collagen degraded ranged from 6.4 +/- 0.4% in skin to 61.6 +/- 5.0% in heart at 1 month of age. During aging the proportion degraded increased in all tissues to maximal values at 15 months, ranging from 56 +/- 7% in skin to 96 +/- 1% in heart. These data suggest that there are marked age-related changes in rates of collagen metabolism. They also indicate that synthesis is active even in old animals, where the bulk of collagens produced are destined to be degraded.

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 The chemistry of the collagen cross-links. The characterization of Fraction C, a possible artifact produced during the reduction of collagen fibres with borohydride

1973 ◽  
Vol 135 (4) ◽  
pp. 657-665 ◽  
Author(s):  
Simon P. Robins ◽  
Allen J. Bailey
Keyword(s):  
Aldol Condensation ◽  
Condensation Product ◽  
Reduced Form ◽  
Borohydride Reduction ◽  
Cross Link ◽  
Collagen Fibres ◽  
Isolation And Identification ◽  
Cross Links

The present paper describes the isolation and identification of a major radioactive component of borotritide-reduced collagen, previously designated Fraction C. The derived structure for the compound confirms that it is identical with the ‘post-histidine’ component described by Tanzer et al. (1973) and given the trivial name histidino-hydroxymerodesmosine. Detailed studies of the effects of acid pH on the formation of Fraction C after borohydride reduction demonstrated the apparent lability of the non-reduced form, thus confirming our previous findings (Bailey & Lister, 1968). Inhibition of the formation of this component by the acid treatment appears to be due to protonation of the histidine imidazole group. Since the only new component formed on reduction of the acid-treated fibres was the reduced aldol condensation product, these results indicate that neither the histidine nor the hydroxylysine residues can be involved in covalent linkage with the aldol condensation product in the native fibre. It is suggested therefore that the proposed non-reduced aldimine form of Fraction C does not exist as an intermolecular cross-link in vivo. Thus the presence of histidino-hydroxymerodesmosine as a tetrafunctional cross-link in reduced collagen fibres is a result of a base-catalysed reaction promoted by the borohydride-reduction procedure and this component must therefore be considered as an artifact.

scholarly journals The chemistry of the collagen cross-links. The absence of reduction of dehydrolysinonorleucine and dehydrohydroxylysinonorleucine in vivo

1971 ◽  
Vol 121 (2) ◽  
pp. 257-259 ◽  
Author(s):  
A. J. Bailey ◽  
Catherine M. Peach
Keyword(s):  
Soft Tissues ◽  
Cross Link ◽  
Collagen Fibres ◽  
Cross Links

Two aldimine bonds have been shown to be present as stabilizing cross-links in intact collagen fibres from soft tissues: dehydrohydroxylysinonorleucine as a major component and dehydrolysinonorleucine being present in trace quantities. In the highly insoluble collagens less dehydrohydroxylysinonorleucine is present but the proportion of dehydrolysinonorleucine increases. In elastin the latter aldimine is reduced in vivo to give a more stable cross-link but no comparable reduction could be detected with either of the aldimines present in collagen.

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 Age-related changes in the physical properties, cross-linking, and glycation of collagen from mouse tail tendon

2020 ◽  
Vol 295 (31) ◽  
pp. 10562-10571 ◽  
Author(s):  
Melanie Stammers ◽  
Irina M. Ivanova ◽  
Izabella S. Niewczas ◽  
Anne Segonds-Pichon ◽  
Matthew Streeter ◽  
...  
Keyword(s):  
The Other ◽  
Cross Linking ◽  
Structural Protein ◽  
Cross Link ◽  
Age Related ◽  
Cross Links ◽  
Tail Tendon ◽  
Collagen Cross Linking ◽  
Age Related Changes ◽  
Tendon Collagen

Collagen is a structural protein whose internal cross-linking critically determines the properties and functions of connective tissue. Knowing how the cross-linking of collagen changes with age is key to understanding why the mechanical properties of tissues change over a lifetime. The current scientific consensus is that collagen cross-linking increases with age and that this increase leads to tendon stiffening. Here, we show that this view should be reconsidered. Using MS-based analyses, we demonstrated that during aging of healthy C57BL/6 mice, the overall levels of collagen cross-linking in tail tendon decreased with age. However, the levels of lysine glycation in collagen, which is not considered a cross-link, increased dramatically with age. We found that in 16-week-old diabetic db/db mice, glycation reaches levels similar to those observed in 98-week-old C57BL/6 mice, while the other cross-links typical of tendon collagen either decreased or remained the same as those observed in 20-week-old WT mice. These results, combined with findings from mechanical testing of tendons from these mice, indicate that overall collagen cross-linking in mouse tendon decreases with age. Our findings also reveal that lysine glycation appears to be an important factor that contributes to tendon stiffening with age and in diabetes.

scholarly journals The Saccharomyces cerevisiae Calponin/Transgelin Homolog Scp1 Functions with Fimbrin to Regulate Stability and Organization of the Actin Cytoskeleton

2003 ◽  
Vol 14 (7) ◽  
pp. 2617-2629 ◽  
Author(s):  
Anya Goodman ◽  
Bruce L. Goode ◽  
Paul Matsudaira ◽  
Gerald R. Fink
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Binding ◽  
Filamentous Actin ◽  
Cortical Actin ◽  
Associated Proteins ◽  
Cross Links ◽  
Biochemical Analyses ◽  
Actin Patch ◽  
The One

Calponins and transgelins are members of a conserved family of actin-associated proteins widely expressed from yeast to humans. Although a role for calponin in muscle cells has been described, the biochemical activities and in vivo functions of nonmuscle calponins and transgelins are largely unknown. Herein, we have used genetic and biochemical analyses to characterize the budding yeast member of this family, Scp1, which most closely resembles transgelin and contains one calponin homology (CH) domain. We show that Scp1 is a novel component of yeast cortical actin patches and shares in vivo functions and biochemical activities with Sac6/fimbrin, the one other actin patch component that contains CH domains. Purified Scp1 binds directly to filamentous actin, cross-links actin filaments, and stabilizes filaments against disassembly. Sequences in Scp1 sufficient for actin binding and cross-linking reside in its carboxy terminus, outside the CH domain. Overexpression of SCP1 suppresses sac6Δ defects, and deletion of SCP1 enhances sac6Δ defects. Together, these data show that Scp1 and Sac6/fimbrin cooperate to stabilize and organize the yeast actin cytoskeleton.

Habitual side-specific loading leads to structural, mechanical and compositional changes in the patellar tendon of young and senior life-long male athletes

2021 ◽  
Author(s):  
Christian Couppé ◽  
Rene B. Svensson ◽  
Sebastian V. Skovlund ◽  
Jacob Kildevang Jensen ◽  
Christian Skou Eriksen ◽  
...  
Keyword(s):  
Patellar Tendon ◽  
Dna Content ◽  
Knee Extensor ◽  
Young Male ◽  
Cross Link ◽  
Cross Sectional ◽  
Specific Loading ◽  
3 Tesla Mri ◽  
Cross Links

Effects of life-long physical activity on tendon function have been investigated in cross-sectional studies, but these are at risk of "survivorship" bias. Here, we investigate if life-long side-specific loading is associated with greater cross-sectional area (CSA), mechanical properties, cell density (DNA content) and collagen cross-link composition of the male human patellar tendon (PT), in vivo. Nine seniors and six young male life-long elite badminton players and fencers were included. CSA of the PT obtained by 3-tesla MRI, and ultrasonography-based bilateral PT mechanics were assessed. Collagen fibril characteristics, enzymatic cross-links, non-enzymatic glycation (autofluorescence), collagen and DNA content were measured biochemically in PT biopsies. The elite athletes had a ≥15% side-to-side difference in maximal knee extensor strength, reflecting chronic unilateral sport-specific loading patterns. The PT CSA was greater on the lead extremity compared with the non-lead extremity (17 %, p=0.0001). Furthermore, greater tendon stiffness (18 %, p=0.0404) together with lower tendon stress (22 %, p=0.0005) and tendon strain (18 %, p=0.0433) were observed on the lead extremity. No effects were demonstrated from side-to-side for glycation, enzymatic cross-link, collagen, and DNA content (50%, p=0.1160). Moreover, tendon fibril density was 87±28 fibrils/μm2 on the lead extremity and 68±26 fibrils/μm2 on the non-lead extremity (28%, p=0.0544). Tendon fibril diameter was 86±14 nm on the lead extremity and 94±14 nm on the non-lead extremity (-9%, p=0.1076). These novel data suggest that life-long side-specific loading in males yields greater patellar tendon size and stiffness possibly with concomitant greater fibril density but without changes of collagen cross-link composition.

scholarly journals Mechanism of protein cleavage at asparagine leading to protein–protein cross-links

2019 ◽  
Vol 476 (24) ◽  
pp. 3817-3834 ◽  
Author(s):  
Michael G. Friedrich ◽  
Zhen Wang ◽  
Kevin L. Schey ◽  
Roger J. W. Truscott
Keyword(s):  
Bond Cleavage ◽  
Peptide Bond ◽  
Human Lens ◽  
Cross Linking ◽  
Protein Cleavage ◽  
Cross Link ◽  
Peptide Bond Cleavage ◽  
Age Related ◽  
Αb Crystallin ◽  
Cross Links

Long-lived proteins (LLPs) are present in numerous tissues within the human body. With age, they deteriorate, often leading to the formation of irreversible modifications such as peptide bond cleavage and covalent cross-linking. Currently understanding of the mechanism of formation of these cross-links is limited. As part of an ongoing study, proteomics was used to characterise sites of novel covalent cross-linking in the human lens. In this process, Lys residues were found cross-linked to C-terminal aspartates that had been present in the original protein as Asn residues. Cross-links were identified in major lens proteins such as αA-crystallin, αB-crystallin and aquaporin 0. Quantification of the level of an AQP0/AQP0 cross-linked peptide showed increased cross-linking with age and in cataract lenses. Using model peptides, a mechanism of cross-link formation was elucidated that involves spontaneous peptide bond cleavage on the C-terminal side of Asn residues resulting in the formation of a C-terminal succinimide. This succinimide does not form cross-links, but can hydrolyse to a mixture of C-terminal Asn and C-terminal Asp amide peptides. The C-terminal Asp amide is unstable at neutral pH and decomposes to a succinic anhydride. If the side chain of Lys attacks the anhydride, a covalent cross-link will be formed. This multi-step mechanism represents a link between two spontaneous events: peptide bond cleavage at Asn and covalent cross-linking. Since Asn deamidation and cleavage are abundant age-related modifications in LLPs, this finding suggests that such susceptible Asn residues should also be considered as potential sites for spontaneous covalent cross-linking.

scholarly journals Collagen cross-linking in human bone and articular cartilage. Age-related changes in the content of mature hydroxypyridinium residues

1988 ◽  
Vol 252 (2) ◽  
pp. 495-500 ◽  
Author(s):  
D R Eyre ◽  
I R Dickson ◽  
K Van Ness
Keyword(s):  
Cortical Bone ◽  
Cancellous Bone ◽  
Human Subjects ◽  
Adult Life ◽  
Bone Collagen ◽  
Cross Linking ◽  
Cross Link ◽  
Age Related ◽  
Cross Links ◽  
And Cartilage

The concentration in collagen of hydroxypyridinium cross-linking amino acids was measured in samples of bone and cartilage from human subjects aged from 1 month to 80 years. Cortical and cancellous bone samples were dissected and analysed separately. In both bone and cartilage, the content of this mature form of cross-link reached a maximum by 10-15 years of age (the amount in cartilage being 5-10 times that in bone), then stayed essentially in the same range throughout adult life. In bone the ratio of the two chemical variants of the mature cross-link, hydroxylysylpyridinoline to lysylpyridinoline, was constant throughout adult life at 3.5:1, whereas in cartilage it was always greater than 10:1. The ratio of hydroxypyridinium cross-links to borohydride-reducible keto-amine cross-links also changed with age. The reducible cross-links in bone collagen decreased steeply in content between birth and 25 years, but persisted in significant amounts throughout adult life. Reducible cross-links had virtually disappeared from cartilage by 10-15 years of age, being replaced by hydroxypyridinium residues, their maturation products. Cancellous and cortical bone collagens showed similar trends with age in their content of mature cross-links, though for each subject the concentration in cancellous bone was always lower than in cortical bone, presumably reflecting the higher turnover rate and hence the more immature state of cancellous bone.

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