The molecular mechanisms involved in the aging of collagen and consequent increase in mechanical strength and stiffness occur in a series of enzymic and non-enzymic intermolecular cross-links. The enzymic mechanism involves divalent aldimine intermolecular cross-links derived from the reaction of aldehydes which then mature to trivalent cross-links and further stabilize the collagen fiber and is now well known. Recent studies have demonstrated that the rate of turnover and level of telopeptide lysyl hydroxylation modifies the nature of the cross-link and hence the mechanical strength of the fiber. The slow turnover of mature collagen subsequently allows accumulation of the products of the adventitious non-enzymic reaction of glucose with the lysines in the triple helix to form glucosyl lysine and its Amadori product, that is, the Maillard reaction. These products are subsequently oxidized to a complex series of advanced glycation end-products, some of which are intermolecular cross-links between the triple helices rendering the fiber too stiff for optimal functioning of the collagen fibers, and consequently of the particular tissue involved. The glycation reactions following maturation are true aging processes, and attempts at their specific inhibition involve competitive inhibition of the Maillard reaction and chemical cleavage of the glycation cross-links. It is clear that the nature of the age-related cross-links and hence tissue strength depends on the rate of turnover of the collagen. An examination of the particular effect of strenuous exercise on the rate of turnover of collagen and hence cross-linking in different tissues could lead to a better understanding of optimal sports training regimes.
The main objectives of the study were to provide an accurate assessment of current levels of old breaks in end-of-lay hens housed in a variety of system designs and identify the important risk factors. Sixty-seven flocks housed in eight broad subcategories were assessed at the end of the production period. Within each flock, the presence of keel fractures was determined and the tibia, humerus and keel bones dissected for measurement of breaking strength. For each house, variations in internal design and perching provision were categorised and the effective heights of the differing structures recorded. All systems were associated with alarmingly high levels of keel damage although variation in mean prevalence between systems was evident with flocks housed in furnished cages having the lowest prevalence (36 per cent) despite also having significantly weaker bones and flocks housed in all systems equipped with multilevel perches showing the highest levels of damage (over 80 per cent) and the highest severity scores.
These changes in the cross-link profile of the intervertebral disc in degenerative disc disease and scoliosis are indicative of increased matrix turnover and tissue remodeling and likely to have implications for the progression of these disorders.
Differential scanning calorimetry has revealed the presence of a new denaturation endotherm at 32°C following UV irradiation of collagen, compared with 39°C for the native triple helix. Kinetic analyses showed that the new peak was a previously unknown intermediate state in the collagen helix-coil transition induced by UV light, and at least 80% of the total collagen was transformed to random chains via this state. Its rate of formation was increased by hydrogen peroxide and inhibited by free radical scavengers. SDS-polyacrylamide gels showed evidence of competing reactions of crosslinking and random primary chain scission. The crosslinking was evident from initial gelling of the collagen solution, but there was no evidence for a dityrosine cross-link. Primary chain scission was confirmed by end group analysis using fluorescamine. Electron microscopy showed that the segment long spacing crystallites formed from the intermediate state were identical to the native molecules. Clearly, collagen can undergo quite extensive damage by cleavage of peptide bonds without disorganizing the triple helical structure. This leads to the formation of a damaged intermediate state prior to degradation of the molecules to short random chains.Studies of the effect of UV radiation on the properties of the collagen molecule, in solution or in its aggregated fiber form, are rather limited. It has been reported that cross-linking and degradation (1) occur on exposure to UV, the relative proportions depending on the presence of oxygen, pH of solution, type of collagen, and wavelength of the UV.These effects have been attributed to absorption by the aromatic groups, phenylalanine and tyrosine, with the suggestion that cross-linking could be mediated through dityrosine crosslinks (2), although no detailed chemistry has been carried out to demonstrate the presence of this cross-link. For example, Kato et al. (3) reported loss of tyrosine and cross-linking in both type I and IV collagens but could not detect dityrosine, only DOPA.1 Kaminska and Sionkowska (4) demonstrated that the infrared amide bands were shifted to a lower frequency, indicating that structural changes were taking place in the molecule. They also deduced that helix-random coil transitions were taking place by reduction in the viscosity (5). Much earlier, Bailey (6) had shown that ionizing-radiation (cobalt 60) reduced the denaturation temperature of collagen solutions in a biphasic manner, and Hayashi et al. (7) reported a similar biphasic phenomenon when collagen was irradiated with UV light during CD measurements.The collagen family of proteins (currently 20) constitute 25% of the total protein mass of the body and determine architecture, tissue strength, and cell-collagen interactions. A characteristic feature of collagen is the triple helical structure of three left-handed polyproline type helices twisted into a righthanded superhelix. The formation of such a structure is due to the repeating sequence Gly-X-Y, where X and Y are often proline and hydroxyproline, respec...
Stiffening of blood vessel walls occurs in the early stages of atherosclerosis, and this process is known to occur earlier in diabetic subjects. The effect could be due, in part, to glycation. Although collagen is responsible for ensuring the ultimate tensile strength of the tissue, elastin largely determines the compliance of the vessel wall in the normal physiological range of pressures and this appears to be closely matched to haemodynamic requirements. Changes in elastin are therefore likely to affect optimal function of the tissue. We have investigated the susceptibility of elastin to glycation and effects of glycation on its mechanical and physicochemical properties. We found that purified elastin and a collagen-elastin preparation from the porcine thoracic aorta rapidly incorporated glucose and ribose, the extent increasing linearly with increasing concentration and reaching a maximum after 7 days at 37 degrees C. Biochemical analysis showed that about one of the five lysines available per elastin monomer was glycated after 12 days incubation at a sugar concentration of 250 mmol/l. In long-term incubations glycation was associated with the appearance of the advanced glycation end products, the fluorescent cross-link pentosidine and the non-fluorescent putative cross-link NFC-1. In both purified elastin and the whole elastin-collagen matrix the slope of the force-extension curve increased significantly with glycation. The greatest increase in stiffness was observed in the elastin-collagen preparation after ribose incubation (250 mmol/l for 1 month), where the slope, at large strain, increased by 56 +/- 19% (mean +/- SD, n = 12). The diameter of the tissue at 1 N force also changed: for elastin there was an increase in length of approximately 5%, but for the elastin-collagen there was a decrease of similar magnitude indicating that glycation introduces differential strains within the fibrous protein matrix. Potentiometric titration demonstrated that glycation was associated both with loss of basic groups and shifts in pK of the acidic groups, which indicated changes in the environment of the charge groups due to conformational rearrangements. Changes in ion binding were dependent on pH, and were consistent with a reduction in effective anionic charge. Calcium binding to elastin was increased at acid pH, but decreased at higher pH. We suggest that these effects are not only due to changes in the charge profile, but also in the conformation of the molecule resulting from glycation of the charged lysine and arginine side-chain residues.
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