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:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The elementary collagen molecule consists of three chains rolled into a spiral and ending in nonhelical telopeptides. In cutaneous collagen, there are two types of chains, in cartilaginous collagen there is only one. In the synthesis, several enzymes play successive parts: proline hydroxylase, lysine hydroxylase, then pro-collagen peptidase and finally, lysine oxidase and hydroxylysine oxidase; their coordinated actions ultimately allow the chains to establish the transverse intra and intermolecular links which give the collagen fiber its cohesion. The type and number of these transverse links vary from one tissue to another. Specific collagenases make collagen degradation possible.
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PMID:[Biochemistry of collagen and the locomoter apparatus (Hereditary connective tissue diseases and rheumatic diseases. Part I]. 1 77

Catechol analogs inhibit the formation of hydroxylysine-derived intermolecular collagen cross links in tissue cultures of chick embryo calvaria. Formation of intermolecular collagen cross links was measured following incorporation of [14C]lysine, reduction with sodium borohydride, and elution from an ion exchange column with a pyridine-formate gradient. Cultures grown in the presence of 10(-3) M catechol, 10(-3) M dopamine, 10(-3) M L-dopa, or 10(-3) M D,L-serine-(2,3,4-trihydroxybenzyl)-hydrazide demonstrated between 43 and 84% inhibition of hydroxylysine formation. Collagen biosynthesis was not diminished in these cultures as compared to controls without additions or with beta-aminopropionitrile when measured by collagenase digestion. The formation of hydroxylysine-derived intermolecular cross links was inhibited 34 to 93% for 5,5'-dihydroxylysinonorleucine and 7 to 71% for 5-hydroxylysinonorleucine. The catechol analogs also inhibit the activity of lysyl hydroxylase as measured by specific tritium release as triated water from an L-[4,5-3H]lysine-labeled unhydroxylated collagen substrate prepared from chick calvaria. Since catechol analogs inhibit the formation of hydroxylysine in a cell-free assay, these compounds must pass into the cells of calvaria in this culture system to inhibit intracellular hydroxylysine formation and subsequently to diminish the reducible intermolecular cross links of the newly synthesized collagen.
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PMID:In vitro inhibition of collagen cross links by catechol analogs. 1 15

Normal mouse spleen cells were fractionated in dishes coated with thin layers of DNP-gelatin or NIP-gelatin, which were insoluble at 4 degrees C. Highly viable cells were recovered from the dishes by melting the gel at 37 degrees C. NIP3- gelatin layers bound approximately 0.1% and DNP4-gelatin layers 0.5% of normal spleen cells. Increasing numbers of low affinity cells were bound with increasing DNP density of the adsorbent. The binding to insoluble DNP-gelatin was hapten-specific since it was inhibited by DNP-lysine, soluble DNP-gelatin or DNP-BSA but not by soluble gelatin or bovine serum albumin (BSA). It was also inhibited by a polyvalent rabbit antimouse Ig. DNP-gelatin was detected on the surface of cells recovered from DNP-gelatin-coated dishes by 125-I-labeled anti-DNP Ig. The cell surface bound DNP-gelatin could be removed by treatment with collagenase. Collagenase treatment did not detectably affect cell viability or surface receptors. More than 90% of DNP-gelatin binding cells were labeled with a polyvalent 125-I-labeled antimouse Ig before or after collagenase treatment under conditions known to label B lymphocytes. Furthermore, the specific antigen-binding capacity of the purified cell populations could be demonstrated after treatment with collagenase. Purified DNP4-gelatin binding cells contained more than 100 times as many DNP-RFC than unfractionated cells. The enrichment of NIP-RFC in the cell population recovered from NIP3 gelatin-coated dishes was more than 200-fold.
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PMID:Separation of antigen-specific lymphocytes. I. Enrichment of antigen-binding cells. 4 91

It is apparent that significant progress has been made in our understanding of the biosynthesis, modifications, and maturation of collagen and elastin. We now recognize and partially understand special reactions involved in hydroxylations within the cell and complex cross-linking processes occurring outside the cell. Recent experiments (191) have shown that in human diploid fibroblast cultures of limited doubling potential (191) the hydroxylation of collagen prolyl residues appears to be "age" or passage-level dependent. With increasing passage level of these cultures, both the ascorbate requirements and the extent of collagen hydroxylation decrease. "Young" cell cultures have a strong requirement for complete hydroxylation and without ascorbate there is only about 50% of the normal level. "Middle-aged" cultures show higher hydroxylation without and full hydroxylation with ascorbate, whereas "old" (or cultures close to "senescence") are incapable of full hydroxylation with or without ascorbic acid. Although the overall system may show some deterioration with increasing passage levels, it appears that with increasing passage levels other components in the cell replace the ascorbate dependence of the hydroxylase system to a greater exten. In some ways, aging WI-38 cultures begin to resemble some transformed cells in their biochemical reactions, although they continue to remain diploid and eventually lose the ability to replicate. It is not yet known whether old animals can produce collagen, which may now be underhydroxylated, perhaps contributing to certain senescent changes. Careful examination of the hydroxylation index of collagen produced in organoid cultures of tissue biopsies as a function of donor age might be informative, particularly if one looks at the quality of collagen by employing collagenase and other proteolytic digests with collagen (191). One could comare the levels of frequent and characteristic peptide triplet sequences such as Gly-Pro-Hyp to Gly-Pro-Pro, Gly-Ala-Hyp to Gly-Ala-Pro, or Gly-Pro-Hyl to Gly-Pro-Lys and others for evaluation of hydroxylation throughout the entire molecule or at selected sequences.
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PMID:Posttranslational protein modifications, with special attention to collagen and elastin. 5 Jun 3

Dacron arterial prostheses, treated or not with biopolymers (gelatin, glycosaminoglycans) were implanted in the abdominal aorta of dogs and the connective tissue synthetised inside and outside the prosthesis was studied. After 3 and 9 months of implantation the prosthesis, a joining portion and a piece of aorta were excised and put in organ culture with 14C-lysine for 3 days. Representative macromolecular extracts were then obtained by a "chemical dissection" procedure. The radioactivity and the chemical composition of these extracts was studied. The DNA content of the prosthesis was higher than that of the adjacent aorta showing a dense cellular repopulation of the prosthesis. This was confirmed by histology also which revealed the presence of a newly formed limiting elastic membrane and the presence of numerous elastic fibrils. Collagen, elastin and glycosaminoglycans could be detected in the macromolecular extracts showing that the cells which repopulated the prosthesis expressed a complete biosynthetic capacity as far as matrix macromolecules are concerned. The distribution of proteins in the extracts was as follows: 4% of total proteins were extracted in a 1M CaCl2-buffer 80% of total proteins in the collagenase extracts, 10% in the 6M urea extract. Only 0,2% of proteins were in the final elastase extract, 10 times less than in the joining aorta fragment. The proportion of the other proteins was similar in aorta and in the prosthesis as well as the chemical composition (hexosamine and hydroxyproline content) of the extracts. The proportion of collagenase-extractable proteins decreased with the time of implantation (from 3 to 9 months) and the proportion of urea-extractable proteins increased. This type of modification is similar to that found in aging aorta wall. 14C-lysine was actively incorporated in all macromolecular fractions studied. The incorporation pattern of the prothesis tissue was similar to that found for the joining host aorta, showing a similar regulatory tendency for matrix macromolecules. It appears therefore that a valid hemocompatible vascular type of connective tissue can be synthesised on the dacron arterial prosthesis and nature of this connective tissue can be influenced by previous biopolymer treatment of the synthetic prosthesis. The described procedure (incorporation of labelled precursors in organ culture) appears to be a valid method for the exploration of the regulatory processes underlying the synthetic capacity for matrix macromolecules of the newly formed tissue in the synthetic prosthesis.
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PMID:Biochemical studies on dacron arterial prostheses. 13 20

Thioglycolate-stimulated mouse peritoneal macrophages secrete a Proteinase which degrades insoluble elastin. There is little elastase activity in cell lysates but the bulk of the enzyme accumulates extracellularly during culture in serum-free medium. The secretion of elastase is sustained for over 12 days in culture and continued secretion of elastase requires protein synthesis. Unstimulated macrophages secrete very little elastase activity but can be triggered to secrete higher levels of this enzyme by phagocytosis and intracellular storage of latex particles. The macrophages elastase is a distinctive proteinase differing from the elastases of pancreas and granulocytes and is distinct from the other secreted proteinases of macrophages, namely, collagenase and plasminogen activator. The macrophages elastase is a serine proteinase and is inhibited by di-isopropyl phosphoro-fluoridate, ovoinhibitor, EDTA, dithiothretiol, and serum. Its activity is little affected by soybean trypsin inhibitor, turkey ovomucoid and chloromethyl ketones derived from tosyl lysine, tosyl phenylalanine, and acetyltetra alanine. Hydrolysis by macrophage elastase of chromogenic ester substrates for pancreatic elastase could not be detected. Elastase secretion by stimulated macrophages exceeds that by primary and established fibroblast cell strains. It is likely that elastase secretion by macrophages plays a major role in the pathogenesis of chronic destructive pulmonary diseases such as emphysema.
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PMID:Elastase secretion by stimulated macrophages. Characterization and regulation. 16 96

The molecule of type I collagen from skin consists of two alpha1(I)-chains and one alpha2-chain. The sequence of the entire alpha1-chain comprising 1052 residues is summarily presented and discussed. Apart from the 279 residues of alpha1(I)-CB8 whose sequence has been established for rat skin collagen, all sequences have been determined for calf skin collagen. In order to facilitate sequence analysis, the alpha1-chain was cleaved into defined fragments by cyanogen bromide or hydroxylamine or limited collagenase digestion. Most of the sequence was established by automated stepwise Edman degradation. The alpha1-chain contains two basically different types of sequences: the triple helical region of 1011 amino acid residues in which every third position is occupied by glycine and the N- and C-terminal regions not displaying this type of regularity. Both of these non-triple helical regions carry oxidizable lysine or hydroxylysine residues as functional sites for the intermolecular crosslink formation. Implications of the amino acid sequence for the stability of the triple helix and the fibril as well as for formation of crosslinks are discussed. Evaluation of the sequence in connection with electron microscopical investigations yielded the parameters of the axial arrangement of the molecules within the fibrils. Axial stagger of the molecules by a distance D = 670 angstrom = 233 amino acid residues results in maximal interaction of polar sequence regions of adjacent molecules and similarly of regions of hydrophobic residues. Ordered aggregation of molecules into fibrils is, therefore, regulated by electrostatic and electrophobic forces. Possible loci of intermolecular crosslinks between the alpha1-chains of adjacent molecules may be deduced from the dimensions of the axial aggregation of molecules.
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PMID:Information contained in the amino acid sequence of the alpha1(I)-chain of collagen and its consequences upon the formation of the triple helix, of fibrils and crosslinks. 17 54

Sequencing of chymotrypsin, trypsin, collagenase- and hydroxylamine-derived peptides, using the automated Edman degradation procedure, yielded the complete amino acid sequence of alpha2-CB4 from calf skin collagen (321 residues). Together with the data from earlier work, an uninterrupted sequence in the helical region of the alpha2-chain from residues 1-393 is now known. Glycine is found in every third position of the peptide. Hydroxylation of proline and lysine occurs only in the Y-position of the triplet Gly-X-Y and is not complete in every position. Some residues, such as glutamic acid, leucine, phenylalanine and arginine, are distributed non-randomly between the X and Y-positions and this non-random distribution is different in the alpha1 and alpha2-chains. Comparison of the N-terminal 393 residues from the helical region of the alpha1 and alpha2-chains revealed a nearly identical distribution of charged polar residues arginine, lysine, glutamic and aspartic acids. The distribution of the triplet Gly-Pro-Hyp is simialr in both chains. The remaining residues in the alpha2-chain exhibit a high degree of substitutions when compared with those in the alpha1-chain. Approximately one in every two residues in both the X and Y-positions are substituted.
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PMID:The covalent structure of collagen. The amino-acid sequence of alpha2-CB4 from calf-skin collagen. 17 31

98% of the collagen in mature connective tissue is in the form of insoluble collagen fibers, consisting of bundles of polymeric collagen (PC) fibrils. The enzymes concerned in connective tissue remodeling degrade PC rather than tropocollagen (TC). TC is the most usual substrate for collagenase assays, and we believe it is essential to employ PC in any study of the activity of collagenolytic enzymes. In order to facilitate the study of enzymic degradation of PC we have labelled PC with fluorescein iso-thiocyanate to produce F-PC fibrils, containing 5 fluorescein labelled epilson-NH2 groups of lysine per TC molecule within the PC. The fluorescent F-PC is degraded at the same rate as PC with the release of hydroxyprolyl peptides but has the great advantage that the solubilised F-peptides can be quantitated by their fluorescent emission. The technique is described in detail employing bacterial collagenase and mammalian collagenase preparations to illustrate the methodology. The advantages of the fluorescent technique over the collagenolytic assay methods currently in use are outlined.
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PMID:Indoluble collagen II. The use of fluorescein labelled polymeric collagen fibrils in a very sensitive assay procedure for enzymes degrading insoluble collagen. 17 6

1. Guinea-pig hepatocytes were prepared by collagenase digestion of the perfused liver. 2. The highest rates of gluconeogenesis were obtained from fructose, followed by pyruvate, xylitol and lactate, glycerol and propionate in that order. Maximum rates of gluconeogenesis were attained at 6-10mm substrate. 3. An initial 15-min lag period occurred during gluconeogenesis from lactate. This lag was abolished by preincubating the cells or by preincubation plus the addition of NH(4)Cl or lysine. 4. The lactate/pyruvate and 3-hydroxybutyrate/acetoacetate ratios were increased during the lag and adjusted to values favouring rapid gluconeogenesis from lactate after 15min. 5. The data suggest that the low glucose synthesis during the lag resulted from a limitation of the glutamate-aspartate shuttle and from the unusual redox state of the NAD(+) couple prevailing during this period. 6. At 0.1mm, amino-oxyacetate, a transaminase inhibitor, decreased gluconeogenesis from lactate by 80%, but had a negligible effect on glucose production from pyruvate. Gluconeogenesis from lactate was also inhibited (20%) by 10mm-dl-3-hydroxybutyrate.
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PMID:Gluconeogenesis by isolated guinea-pig liver parenchymal cells. 17 3


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