Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two different subendothelial macromolecules have been identified as being thrombogenic: collagen and the microfibrils associated with elastin. The interaction between platelets and collagen involves the binding of platelet membrane receptors by numerous sites repeatedly staggered along a collagen fiber: this explains why the preservation of ordered structures (quaternary and tertiary structures) is so important in the reactivity of collagen towards platelets. In the case of Type III collagen, a nonapeptide has been identified as possibly being part of these repetitive sites. The microfibrils have not yet been characterized, although the biochemical data presently available show that they are acidic glycoproteins resistant to collagenase. Microfibrils extracted from human placenta or bovine aorta induce the aggregation of platelets in a reaction which involves platelet glycoprotein Ib and FVIII/vWF. A general model proposed for explaining platelet adhesion to subendothelium suggests that two different mechanisms should be envisaged depending on the thrombogenic macromolecules (collagen, microfibrils) involved.
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PMID:The molecular interaction between platelet and vascular wall. 622 98

Thrombogenicity of the vessel wall: role of the microfibrils and collagen. The study of platelet adhesion to rabbit aortic subendothelium preincubated with highly specific collagenase has revealed that platelets adhere to the microfibrils of the elastic lamina. To certify that an interaction between microfibrils and platelets can occur, microfibrils from two different origins were isolated: placental microfibrils extracted from the villi of human placenta, and aortic microfibrils extracted from adult bovine aorta. Both preparations were histologically homogeneous, and differed in their amino acid composition with an acidic character more pronounced for placental than for aortic microfibrils. Both preparations were able to induce platelet aggregation in plasma, but not after platelet isolation and resuspension in buffer. An interesting feature was the fact that when normal platelets were isolated, washed and resuspended in plasma from severe VWD patients, they were not aggregated by placental or aortic microfibrils. This defect was corrected after perfusion of cryoprecipitate to one patient. Moreover, monoclonal antibody directed against platelet glycoprotein Ib inhibited the aggregation of platelets to microfibrils, not to collagen; this suggested that an axis platelet GPI-FVIII/VWF-microfibrils could represent a pathway for platelet/subendothelium interaction. The adhesion of platelets to collagen seems to involve the staggering of a short amino acid sequence along a collagen fibre. This possibility arises from the requirement for the preservation of the quaternary structure of collagen in the induction of platelet adhesion/aggregation in vitro, and also from the identification and synthesis of a nonapeptide derived from type III collagen, which is also to specifically inhibit the aggregation of platelets by collagen, following its binding to platelet membrane.
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PMID:[Thrombogenicity of the vessel: role of microfibrils and of collagen]. 698 59

Collagenase-1 (C1) is the predominant matrix metalloproteinase present in newly formed microvessels and serves as a marker of neovascularization. The expression of the oncofetal fragment of fibronectin (Fn-f) was found to be increased during angiogenesis. In the present study, we investigated the relationship between the expression of collagenase-1 and the oncofetal fragment of fibronectin in newly formed microvessels as markers of tumor angiogenesis. In aggressive skin tumors (i.e., morpheaform and recurrent basal cell carcinomas) and squamous cell carcinomas, neovascularization was associated with a marked increase in the number of C1-positive and Fn-f-positive microvessels. At the beginning of elongation, microvessels begin to produce C1 but lose their ability to express type IV collagen and FVIII-related antigen. Later, this endothelium produces both Fn-f and C1. As maturation of microvessels occurs, C1-containing endothelium fails to express Fn-f but begins to produce a type IV collagen-containing basement membrane and FVIII-related antigen. These studies show that there is a selective expression of both Fn-f and collagenase by immature endothelial cells. C1 production begins at early stages of blood vessel formation and continues throughout angiogenesis. In contrast, Fn-f expression is limited to later stages of vasculogenesis, indicating that these proteins are reliable markers of angiogenesis.
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PMID:Interstitial collagenase and the ED-B oncofetal domain of fibronectin are markers of angiogenesis in human skin tumors. 972 25

Penetration of adhesives into the demineralized dentin surface and their subsequent conversion are critically important to longevity of the adhesive resin (AR)-dentin bond. The durability of the resin-dentin bond is investigated by monitoring the change of adhesive concentration within the hybrid layer (HL) of aged specimens using Raman spectroscopy. Absolute molar concentrations of Bis-GMA and HEMA were measured across the HL of resin-dentin specimens 24 h after photopolymerization and after 24-week storage in one of three media: artificial saliva (SAL), SAL containing cholesterol esterase to attack resin (EST), and SAL containing bacterial collagenase to attack collagen (COL). No significant difference among these groups for both Bis-GMA and HEMA molar concentrations at 24-h storage was found; however, concentrations decreased from the AR to the middle of the HL. Concentrations remained unchanged at any resin-dentin position after aging in SAL. In the HL, concentrations significantly decreased with aging in COL and tended to decrease in EST. While showing potential enzymatic biodegradative effects of endogenous matrix metalloproteinases and salivary esterases, this methodology may also prove to be a valuable assessment of new chemistries and future approaches to improve resin-dentin bond performance. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.
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PMID:In vitro enzymatic biodegradation of adhesive resin in the hybrid layer. 2012 99

Corneal melting is an uncontrolled, excessive degradation of cellular and extracellular components of the cornea. This potential cause of corneal blindness is caused by excessive expression of zinc-dependent matrix metalloproteinases (MMPs) and has no satisfying cure as of now. Herein, we introduce a novel therapeutic hydrogel which can be made into a contact lens to slow down the progression of corneal melting by deactivating MMPs. The hydrogel backbone is comprised of poly(2-hydroxyetyl methacrylate) (pHEMA), a main material for commercial contact lenses, and dipicolylamine (DPA) which has high affinity and selectivity towards zinc ion. Due to the high affinity towards zinc ions, the DPA-conjugated pHEMA (pDPA-HEMA) hydrogel selectively removes zinc ions from a physiological buffer and deactivates MMP-1, MMP-2 and MMP-9 within 2 hours. pDPA-HEMA hydrogel also effectively prevents degradation of porcine corneas by collagenase A, a zinc-dependent protease, whereas the corneas completely degrades within 15 hours when incubated with pHEMA hydrogel. The presence of pDPA-HEMA hydrogel does not affect the viability of keratocytes and corneal epithelial cells. Unlike the conventional MMP inhibitors (MMPi), the pDPA-HEMA hydrogel minimizes the risk of serious non-specific side effects, and provides a method to slow down the progression of corneal melting and other related ocular diseases.
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PMID:Matrix Metalloproteinase-Deactivating Contact Lens for Corneal Melting. 3169 98