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)

To clarify the relationship of the 290 and 145 kDa chains of the epidermolysis bullosa acquisita (EBA) antigen, we subjected urea extracts of skin basement membrane zone (BMZ) proteins and isolated 290 and 145 kDa chains of the EBA antigen cut out of sodium dodecyl sulfate polyacrylamide gels to treatment with clostridial collagenase. When the reaction products were electrophoresed, transblotted, and reacted with EBA patient sera or two monoclonal antibodies to the EBA antigen, the 290 kDa chain was degraded into the 145 kDa band that was resistant to cleavage with collagenase. The 145 kDa domain, isolated after collagenase treatment of the whole BMZ extract, was resistant to degradation by hyaluronidase, chondroitinase ABC, heparinase, and heparitinase but was readily degraded by V-8 protease. These data suggest that the EBA antigen consists of collagen and noncollagen domains of identical size (Mr 145,000), and that the 145 kDa noncollagen domain is generated via degradation of the native 290 kDa species by collagenase.
J Invest Dermatol 1988 Feb
PMID:Epidermolysis bullosa acquisita antigen: relationship between the collagenase-sensitive and -insensitive domains. 282 79

In order to investigate the role of inflammatory cells in altering the collagenase production by epidermolysis bullosa (EB) fibroblasts, macrophage and polymorphonuclear leukocyte (PMN) factors obtained from mouse peritoneal fluids were added to the fibroblast culture system, and collagenase activity was assayed after a 48-h incubation. Data obtained here revealed that the response of collagenase production by fibroblasts was quite different, depending on the type of EB. Namely, EB dystrophica recessiva (EBDR) (n = 2) fibroblasts produced significant amounts of collagenase in the range of 5.07 (U/ml) to 6.04 in response to macrophage-conditioned medium, macrophage lysate, and PMN lysate, compared with 0.13 in the absence of these. On the other hand, EB dystrophica dominans (EBDD) (n = 1) fibroblasts showed little or no overt increase in enzyme production in the presence of macrophage lysate and PMN lysate, which resulted in a moderate increase to 3.82 in response to macrophage-conditioned medium. Furthermore, EB simplex (EBS) (n = 1) fibroblasts produced collagenase up to 3.84 in response to these three factors. These factors can be inactivated by treating with trypsin, pronase, and phenylglyoxal. Our data clearly indicated that, in the comparisons of EBDD and EBS fibroblasts, EBDR fibroblasts showed quite high response to factors derived from macrophages and PMNs in terms of collagenase production. This fact may raise a clue that accounts for the high levels of tissue collagenase activity, which plays a potentially major role in blister formation in EBDR.
J Invest Dermatol 1988 Feb
PMID:Response of epidermolysis bullosa fibroblasts to factors derived from macrophages and polymorphonuclear leukocytes in terms of collagenase production. 282 81

The pathophysiology of tissue fragility in recessive dystrophic epidermolysis bullosa may be due in part to excessive destruction of interstitial collagens by a structurally altered, but catalytically active, form of human skin collagenase. Therapeutic attempts directed toward reducing the expression of this enzyme have resulted in clinical improvement in some patients with the disease.
Arch Dermatol 1988 May
PMID:A perspective on the role of collagenase in recessive dystrophic epidermolysis bullosa. 283 15

Phenytoin has been proposed for the treatment of certain dermatologic conditions involving connective tissue abnormalities. To understand the biochemical basis of connective tissue changes, we incubated human skin fibroblasts in culture with varying concentrations of phenytoin. The results indicated that fibroblast proliferation, detected by tritiated thymidine incorporation into cells, was slightly stimulated when short incubation periods and low concentrations of phenytoin were employed. However, with longer incubation times and higher phenytoin concentrations, a significant reduction in fibroblast proliferation was observed. Further studies demonstrated that incubation of cells with phenytoin did not affect the production of procollagen, measured as synthesis of radioactive hydroxyproline in the cultures. However, assay of prolyl hydroxylase, an enzyme participating in the post-translational synthesis of hydroxyproline during collagen biosynthesis, was significantly reduced in the fibroblast cultures. The activity of collagenase, an enzyme participating in degradation of collagen, was markedly decreased in cultures treated with phenytoin. Thus, phenytoin may modulate collagen metabolism primarily by affecting the degradation of collagen. The results support previous suggestions that phenytoin may be useful for treatment of patients with increased levels of collagenase, such as in recessive dystrophic epidermolysis bullosa.
Arch Dermatol 1985 Jan
PMID:Phenytoin modulates connective tissue metabolism and cell proliferation in human skin fibroblast cultures. 298 18

Filamentous aggregates of collagen are distinct structures in the pathological dermis. These aggregates are distinguishable from fibrous long-spacing collagen (in vitro and at biopsy) and the Luse body. The aggregates are produced from dermal collagen fibrils by clostridial collagenase and culture-medium extract, which supposedly contains cellular collagenase at a neutral pH, as well as by organ cultures. In vitro experiments showed that carrageenan granuloma contains fibrous long-spacing collagen and segment long-spacing collagen. The granuloma also contains the aggregates. The aggregates were found in skin biopsies from syphilitic chancres, acrosclerotic scleroderma, morphea, mycosis fungoides, myeloid leukemia, mastocytosis and malignant melanoma. These findings indicate that the aggregates are products of the in situ degradation of collagen fibrils by some collagenolytic factor. This factor may originate in fibroblast-like cells, reticulum cells, leukemia cells, mast cells and melanoma cells.
Arch Dermatol Res 1985
PMID:Filamentous aggregates of collagen. Ultrastructural evidence for collagen-fibril degradation in situ. 299 Mar 57

Our previous studies of human basal cell carcinomas (BCC) revealed increased skin collagenase in vivo. Immunocytochemically the collagenase was localized to adjacent stroma, not to the tumor cells. When grown in culture, skin fibroblasts derived from tumor stroma showed a 3- to 4-fold increase in collagenase for the first 10-14 mean population doublings, after which collagenase expression reverted to control levels. These studies suggested that tumors stimulated adjacent fibroblasts to produce more collagenase. In the present study we sought direct evidence for epithelial-stromal interaction in this neoplasm. Under dissecting microscopy tumor islands were freed of stroma, homogenized, sonicated, and centrifuged to remove insoluble tissue. Tumor extracts were incubated with monolayer cultures of normal human skin fibroblasts to assess their effect on collagenase synthesis in these target cells. Culturing the fibroblasts for 24 h in the presence of individual BCC extracts resulted in a 1.6- to 3-fold increase in trypsin-activatable collagenase in the culture medium. This was paralleled by an equal increase in immunoreactive protein, suggesting enhanced enzyme synthesis. There was no change in the activity per immunoreactive protein, indicating a catalytically unaltered enzyme. Gel filtration of pooled BCC extracts showed that the stimulatory activity was contained in eluent fractions of Mr approximately 19Kd. These data suggest that BCCs elaborate a macromolecular cytokine that induces collagenase synthesis in skin fibroblasts and emphasize the importance of epithelial-stromal interactions in cutaneous tumor invasion.
J Invest Dermatol 1985 Aug
PMID:Stimulation of skin fibroblast collagenase production by a cytokine derived from basal cell carcinomas. 299 91

Excess vitamin A has striking morphologic and developmental effects on chick embryo skin. While cytoplasmic retinoic acid-binding protein (CRABP) was known to be abundant in chick embryo skin, neither quantitative values nor the distribution between dermis and epidermis have been established. We determined CRABP levels in collagenase-separated dermis and epidermis from 8-day-old embryos using specific binding of all-trans-[11-3H]retinoic acid in cytosols prepared from gram quantities of these tissues. The level of CRABP in dermis was twice the level in epidermis whether calculated on the basis of wet weight, cytosol protein, or DNA. When averaged over many preparations, 3 times as much dermis as epidermis was recovered from a single piece of skin. Therefore, the dermis contained 85% of the extremely high CRABP levels found in collagenase-treated skin, while epidermis contributed only 15%. Cytoplasmic retinol binding protein (CRBP) was also detected in chick embryo skin, but the binding was low and the levels in epidermis and dermis were not significantly different. The amount of CRABP in chick embryo skin (1600 pmol/g wet weight or 100 pmol/mg cytosol protein) is the highest level reported in any tissue and suggests an important role for vitamin A in the normal development and maturation of skin.
J Invest Dermatol 1985 Sep
PMID:Cytoplasmic vitamin A binding proteins in chick embryo dermis and epidermis. 299 28

Proteolytic enzymes may be involved in blister formation in dermatitis herpetiformis (DH). We have examined collagenase, gelatinase and elastase-like enzyme activities in fluids collected from spontaneous blisters and from suction blisters raised on developing DH-lesions induced by application of potassium iodide. Control suction blisters were raised on unaffected DH-skin and on healthy volunteers. High enzyme activities were found in spontaneous blisters, and suction blister fluids obtained from developing lesions showed increased levels of gelatinase and elastase-like enzymes. Inhibitor studies revealed that a part of the elastase-like enzyme activity might be derived from inflammatory cells. Gel filtration chromatography disclosed two separate elastase-like enzymes which, as they had high molecular weights, could be either enzyme-inhibitor complexes or aggregates.
Br J Dermatol 1986 Mar
PMID:Proteolytic enzymes in blister fluids from patients with dermatitis herpetiformis. 300 37

The interaction of connective tissue stroma and epithelial cutaneous cancer is an active area of investigation in dermatology. Studies summarized here explore the role of collagenase in basal cell carcinoma (BCC) invasiveness. Evidence is presented to support the role of a cytokine or cytokines secreted by BCCs that stimulate collagenase production by surrounding stromal fibroblasts. Prospects for further research in this area are proposed.
J Dermatol Surg Oncol 1986 Aug
PMID:Basal cell carcinoma and collagenase. 301 54

A 33-year-old man presented with a spontaneous progressive cutaneous tumor-like fibrosis involving the right leg and buttock. Histologically the deep dermis was composed of numerous fibroblasts and dense bands of collagen, suggesting that the lesion might be related to an abnormality in collagen metabolism. Fibroblast cultures were established from the affected and normal-appearing skin. The growth rate of the lesional cells was essentially equal to that of control cells. The synthesis of procollagen was approximately 3.5-fold increased in the cells derived from the nodules when compared with control fibroblasts (p less than 0.001). The increase in procollagen synthesis was reflected by an approximate 6-fold increase in both type I and type III procollagen mRNA abundance in the lesional fibroblasts (p less than 0.001), thus suggesting an aberration in the pretranslational level of procollagen gene expression. In contrast, the synthesis of collagenase, the enzyme required for the initiation of collagen degradation, was decreased to approximately 25% of control values (p less than 0.0025), although the enzyme was catalytically normal. The data indicate that these cells are characterized by an increased synthesis of procollagen and decreased synthesis of collagenase, 2 phenotypic characteristics that could account pathophysiologically for the lesions. The unusual reciprocal nature of these biochemical parameters in 2 proteins important in connective tissue homeostasis suggests that this progressive tumor-like condition may have resulted from the expansion of a clonal population of cells.
J Invest Dermatol 1986 Aug
PMID:Progressive nodular fibrosis of the skin: altered procollagen and collagenase expression by cultured fibroblasts. 301 1


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