Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Solubilized interstitial collagens will form a fibrillar, gel-like lattice when brought to physiologic conditions. In the presence of human dermal fibroblasts the collagen lattice will contract. The rate of contraction can be determined by computer-assisted planemetry. The mechanisms involved in contraction are as yet unknown. Using this system it was found that the rate of contraction was markedly decreased when collagen lacking telopeptides was substituted for native collagen. Histidinohydroxylysinonorleucine (HHL) is a major stable trifunctional collagen cross-link in mature skin that involves a carboxyl terminal, telopeptide site 16c, the sixteenth amino acid residue from the carboxy terminal of the telopeptide region of alpha 1 (I) in type I collagen. Little, if any, HHL was present in native, purified, reconstituted, soluble collagen fibrils from 1% acetic acid-extracted 2-year-old bovine skin. In contrast, HHL cross-links were present (0.22 moles of cross-link per mole of collagen) in lattices of the same collagen contracted by fibroblasts. However, rat tail tendon does not contain HHL cross-links, and collagen lattices made of rat tail tendon collagen are capable of contraction. This suggests that telopeptide sites, and not mature HHL cross-links per se, are essential for fibroblasts to contract collagen lattices. Beta-aminopropionitrile fumarate (BAPN), a potent lathyrogen that perturbs collagen cross-linking by inhibition of lysyl oxidase, also inhibited the rate of lattice cell contraction in lattices composed of native collagen. However, the concentrations of BAPN that were necessary to inhibit the contraction of collagen lattices also inhibited fibroblast growth suggestive of cellular toxicity. In accordance with other studies, we found no inhibition of the rate of lattice contraction when fibronectin-depleted serum was used. Electron microscopy of contracted gels revealed typical collagen fibers with a characteristic axial periodicity. The data provide evidence that collagen telopeptide sites play a role in collagen gel lattice contraction.
 ...
PMID:Collagen telopeptides (cross-linking sites) play a role in collagen gel lattice contraction. 187 57

Electrostatic energies of interaction between type I collagen molecules were calculated, using models developed by Timasheff and Hill. These energies, along with a contribution from hydrophobic forces, were then incorporated into an equation due to Flory that described phase equilibria of rod-like polymers. The Flory formalism in turn permitted a calculation of the overall free energy of fibril formation (delta Ff), and an assessment of the relative contribution of electrostatic and hydrophobic forces to delta Ff. Lastly, delta Ff was used in a nucleation-growth model relating halftimes of fibril formation (t1/2) to ionic strength (I) and temperature. Because the theory provided no basis for setting absolute levels of the energetic contributions, five parameters in the model had to be derived from experimental data. Based on the fit of theory to experimental results both for intact and pepsinized collagen, it was found that very low electrostatic energies (about -1 kcal/mole per collagen molecule) were sufficient to explain experimental t1/2 vs I relationships. This energy is equivalent to 1 close charge-pair interaction per molecule and appears to be lower than the energy assignable to hydrophobic interactions.
 ...
PMID:The relative contribution of electrostatic interactions to stabilization of collagen fibrils. 236 12

Male white Leghorn chickens were exercised on a treadmill at 70-80% of their maximal oxygen consumption starting at 4 weeks and continuing up to 20 weeks of age. The effect of the strenuous exercise regime on the extracellular matrix of menisci was followed through studies of proteoglycans and collagen. Avian menisci contain type I collagen, chondroitin sulfate proteoglycans, which increase with age in amount and degree of aggregation, and dermatan sulfate proteoglycans, which decrease with age. Five weeks of exercise cause a premature decrease of dermatan sulfate proteoglycans, while the chondroitin sulfate-containing molecules become significantly more aggregated than those of the tissue of age-matched controls. Strenuous exercise also causes a significant decrease in the number of pyridinoline crosslinks per mole of collagen in the menisci of young runners. The exercise-induced changes of proteoglycan and collagen occur only during the period of active growth, and all parameters return to normal when the animals reach skeletal maturity. The early proteoglycan aggregation and dermatan sulfate decrease induced by exercise are probably an adaptation to the increased loading. Although the mechanism by which strenuous exercise reduces or delays the formation of collagen pyridinoline crosslinks in menisci of skeletally immature animals is unknown, their decrease could negatively affect the mechanical properties of the tissue during the period of active growth.
 ...
PMID:Response of immature chicken meniscus to strenuous exercise: biochemical studies of proteoglycan and collagen. 312 12

Dermal fibrosis, characterized by collagen accumulation, is the hallmark of several cutaneous diseases. To examine the mechanisms of collagen deposition in fibrotic skin diseases, fibroblast cultures were established from the skin of patients with progressive systemic sclerosis, morphea, scleredema, familial cutaneous collagenoma, connective tissue nevi of the collagen type, or keloids; these patients served as prototypes of fibrotic skin diseases with varying clinical features and potentially different etiologic factors. Collagen production was assayed by the synthesis of [3H]hydroxyproline, and types I and III procollagen messenger RNA (mRNA) levels were determined by dot blot hybridizations using human type I and type III procollagen-specific cDNA probes. The collagen production in fibroblast cultures from the fibrotic diseases was increased up to 6-fold over the controls, and a relatively good correlation between the collagen production and type I collagen mRNA levels was noted. The type I/III procollagen mRNA ratio in control fibroblast cultures was 5.9 +/- 1.6 (mean +/- SD). The corresponding ratio in keloid cell culture was markedly increased, while slightly decreased values were noted in the case of morphea and familial cutaneous collagenoma; the values in other cultures were within the normal range. The results suggest that procollagen production in fibroblast cultures derived from fibrotic skin diseases reflects elevated levels of the corresponding procollagen mRNA. The increased mRNA abundance, suggesting pretranslational control, may result from enhanced transcriptional activity of the corresponding gene or alternatively reflects increased stability of the mRNA molecule.
 ...
PMID:Regulation of collagen gene expression in cutaneous diseases with dermal fibrosis: evidence for pretranslational control. 358 56

A 10-yr-old female presented with cerebriform tumors covering the plantar surfaces of both feet. Histologically, the lesions consisted of thick collagen fibers and the content of collagen per surface area of skin was increased about 8-fold. Examination of the collagen by SDS-polyacrylamide gel electrophoresis, after limited pepsin proteolysis, showed that the lesions consisted almost exclusively of type I collagen, the predominant collagen type in human skin. Thus, a diagnosis of connective tissue nevi of the collagen type was made. Fibroblast cultures were established from the affected and normal-appearing areas of the skin, and examined for the rate of collagen synthesis, production of collagenase and growth kinetics of the cells. Cell cultures derived from the lesion and from control skin synthesized procollagen at the same rate and in a normal type I/type III procollagen ratio. However, the production of enzymatically active and immunologically detectable collagenase was reduced by 70-82% in the cultures derived from the lesion as compared to controls (p less than 0.005). Fibroblasts derived from the lesions also displayed a mean population doubling time of 1.17 +/- 0.08 days compared to 1.83 +/- 0.24 and 1.92 +/- 0.09 days for control cell strains and cells derived from normal skin of the patient, respectively (p less than 0.025). These results suggest that the excessive deposition of collagen in this case may have resulted from decreased local degradation of collagen. Enhanced proliferative capacity of the regional fibroblasts may have contributed to the accumulation of collagen in these lesions.
 ...
PMID:Decreased collagenase production by regional fibroblasts cultured from skin of a patient with connective tissue nevi of the collagen type. 627 72

The elusive dermal neurocristic effector cell is identified by its expression of fibrogenic functions in a variety of cutaneous neurocristic dysplasias and neoplasms. It is a normal resident of the dermis that disguises its embryonic heritage by the acquisition of fibrocytic (or fibrohistiocytic) functions. It shares with other cutaneous neurocristic derivatives the capacity to express variably three basic functions: 1) fibrogenesis, 2) melanogenesis, or 3) neurosustentation in the manner of the supportive cells of peripheral nerves. Its role in developing skin is prominently displayed in congenital nevi. The fibrogenic potentials of its embryonic relatives, the neurosustentacular cells and melanocytes, are expressed in perineurial fibromas and desmoplastic malignant melanomas. In the latter neoplasms, neurosustentacular functions are also often displayed. In the normal skin, the potentials of the cutaneous neurocristic migrants are usually restricted to one of three options. In dysplasias, the controls are derepressed and migrations may offer new, environmental influences that favor expression of latent properties. A dysplastic melanocyte loses the primary epigenic influence of epithelium by migration into the dermis. In the dermis, it encounters peripheral nerves and mesenchyme. In response, it may express its latent fibrogenic or neurosustentacular possibilities. The dermis is neuromesenchyme. The adventitial dermis is a special adaptation of mesenchyme to the metabolic needs of epithelium. Melanocytes and Merkel cells are situated ideally to function as mediators between epithelium and dermis. Pigmented melanocytes that concentrate in the bulbs of growing hairs probably are more important as mediators of epithelial-mesenchymal reactions than as sources of pigment. The reticular dermis and retinacula represent transformation from fetal type III collagen to adult type I collagen. In Mongolian spots, melanocytes are confined to the reticular dermis. They identify neurocristic effector cells that have been diverted from fibrogenic to melanogenic functions. In all likelihood, the transformation in the dermis from type III to type I collagen is induced by neurocristic migrants that have lost their identity in the population of fibrocytic cells.
 ...
PMID:Neuromesenchyme. The concept of a neurocristic effector cell for dermal mesenchyme. 631 35

Collagens of the ligamentum teres of the femur and the hip joint capsule of 14 patients with congenital dislocation of the hip (CDH) were studied biochemically. Collagen was a major component of these tissues. Solubility of collagen was reversely related to age except in two cases. Collagen of both ligamentum teres of the femur and hip joint capsule was composed of type I, III and V collagens except in three cases. In these three cases with nevus or general joint laxity, two additional collagenous components were also found. The ratios of type III collagen to type I collagen were increased in CDH except in one case with short stature. These abnormalities of collagen metabolism could be the underlying cause of CDH and other clinical symptoms in these patients.
 ...
PMID:Soft tissue collagen in congenital dislocation of the hip. Biochemical studies of the ligamentum teres of the femur and the hip joint capsule. 647 May 41

The relative percentage of type III to type I collagen, the ratio of alpha 1(I) to alpha 2(I) collagen chains and the ratio of dimers (beta-chains) to monomers (alpha-chains) in type I collagen have been measured in solubilized collagen fractions from keloids and hypertrophic scars aged about 1-7 years after burn. In tissue samples the content of crosslink with structure of pyridinoline were analyzed and expressed as mole of crosslink per mole of collagen. A comparison between hypertrophic and keloid scars has shown that the young (about 1 year) hypertrophic scars have higher ratios alpha 1(I)/alpha 2(I) and beta 11 + beta 12/alpha 1(I) + alpha 2(I). The increased proportion of beta-chains in the younger hypertrophic scars approximated to the same level as in normal skin within 7 years after lesion. There was no decrease in the ratio dimers/monomers of collagen type I with age of keloid scar tissue. The relative amount of collagen type III in young keloid scars was found decreased as compared to age-matched hypertrophic scars (13 +/- 3 and 17 +/- 7 respectively), but was similar in the older scars. The average pyridinoline crosslinks content per mole of collagen in keloids was 2 times as high as in hypertrophic scars. The data support the suggestion that general, as well as peculiar disturbances of collagen metabolism are involved in the development of keloids and hypertrophic scars.
 ...
PMID:[Comparative study of collagen in hypertrophic and keloid cicatrix]. 913 58

Keloid is a tissue with an excessive accumulation of collagen. In this study, we have partially characterized post-translational modifications of type I collagen in human keloid in order to pursue their potential involvement in this pathology. The levels of lysyl hydroxylation of the helical portions of alpha 1 and alpha 2 chains of type I collagen in keloid were significantly higher than those of normal, while the levels of prolyl hydroxylation were identical between these two groups. The contents of the major reducible cross-links in dermal collagen, dehydro-hydroxylysinonorleucine and dehydro-histidinohydroxymero-desmosine, were both significantly higher in keloids (up to sixfold) than those of normal. In addition, significant amounts of hydroxylysine-aldehyde derived cross-links that are characteristic of skeletal tissue collagens, dehydro-dihydroxylysinonorleucine (about 0.3 mole/mole of collagen) and pyridinoline (about 0.1 mole/mole of collagen), were found in keloids. These results indicate that keloid-forming cells are phenotypically different from those in normal dermis and that the collagen produced is highly cross-linked. The increased cross-linking provides the fibrils with more stability that may result in an accumulation of collagen.
 ...
PMID:Altered posttranslational modifications of collagen in keloid. 973 Nov 91

Cortical and trabecular bone have similar creep behaviors that have been described by power-law relationships, with increases in temperature resulting in faster creep damage accumulation according to the usual Arrhenius (damage rate approximately exp (-Temp.-1)) relationship. In an attempt to determine the phase (collagen or hydroxyapatite) responsible for these similar creep behaviors, we investigated the creep behavior of demineralized cortical bone, recognizing that the organic (i.e., demineralized) matrix of both cortical and trabecular bone is composed primarily of type I collagen. We prepared waisted specimens of bovine cortical bone and demineralized them according to an established protocol. Creep tests were conducted on 18 specimens at various normalized stresses sigma/E0 and temperatures using a noninvasive optical technique to measure strain. Denaturation tests were also conducted to investigate the effect of temperature on the structure of demineralized bone. The creep behavior was characterized by the three classical stages of decreasing, constant, and increasing creep rates at all applied normalized stresses and temperatures. Strong (r2 > 0.79) and significant (p < 0.01) power-law relationships were found between the damage accumulation parameters (steady-state creep rate d epsilon/dt and time-to-failure tf) and the applied normalized stress sigma/E0. The creep behavior was also a function of temperature, following an Arrhenius creep relationship with an activation energy Q = 113 kJ/mole, within the range of activation energies for cortical (44 kJ/mole) and trabecular (136 kJ/mole) bone. The denaturation behavior was characterized by axial shrinkage at temperatures greater than approximately 56 degrees C. Lastly an analysis of covariance (ANCOVA) of our demineralized cortical bone regressions with those found in the literature for cortical and trabecular bone indicates than all three tissues creep with the same power-law exponents. These similar creep activation energies and exponents suggest that collagen is the phase responsible for creep in bone.
 ...
PMID:Results from demineralized bone creep tests suggest that collagen is responsible for the creep behavior of bone. 1021 62


1 2 Next >>