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)

Photopolymerizable polyethylene glycol (PEG) derivatives have been investigated as hydrogel tissue engineering scaffolds. These materials have been modified with bioactive peptides in order to create materials that mimic some of the properties of the natural extracellular matrix (ECM). The PEG derivatives with proteolytically degradable peptides in their backbone have been used to form hydrogels that are degraded by enzymes involved in cell migration, such as collagenase and elastase. Cell adhesive peptides, such as the peptide RGD, have been grafted into photopolymerized hydrogels to achieve biospecific cell adhesion. Cells seeded homogeneously in the hydrogels during photopolymerization remain viable, proliferate, and produce ECM proteins. Cells can also migrate through hydrogels that contain both proteolytically degradable and cell adhesive peptides. The biological activities of these materials can be tailored to meet the requirements of a given tissue engineering application by creating a mixture of various bioactive PEG derivatives prior to photopolymerization.
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PMID:Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: synthetic ECM analogs for tissue engineering. 1157 79

Despite the anti-TNF alpha based progress in the treatment of RA, it is necessary to further optimize study designs and reports (Etanercept/MTX combination with results of radiological progression; publication of D2E7 trials; combination of D2E7 with MTX). Moreover, innovative immunobiologicals (PEG-TNFRI, PEG-TNF alpha antibody fragments, soluble TNFRI, CTLA4-Ig, CD40 ligand antibody, antibodies against IFN-gamma, IL-6, IL-12, IL-15, IL-18, complements), inhibitors of TNF alpha translation (peptides, anti-sense constructs) or TNF alpha synthesis (targeting NF kappa B, p38 MAP-kinase, phosphodiesterase IV, TNF alpha converting enzyme) are forthcoming. Principally different are inhibitors of complement convertases or collagenase as well as vaccination studies or trials trying to induce T cell anergy. Furthermore, for patients with MTX side effects, alternative DMARDs need to be tested along with TNF alpha blockers. Combination studies of TNF alpha constructs with other immunobiologicals (anti-CD4, IL-4, IL-10, IL-1RA) should be evaluated. To date, TNF alpha blockers have been evaluated in very early RA. Finally, a step-down trial will test whether--after induction of remission with a TNF alpha blocker plus MTX--replacement of the TNF alpha blocker with MTX alone or in combination with leflunomide will be able to keep disease activity suppressed for a longer duration.
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PMID:[New therapy developments in rheumatoid arthritis]. 1175 32

Preantral follicles mechanically isolated from the ovaries of 12-day-old mice were exposed to 2 mol ethylene glycol l(-1) for 2 or 5 min and then to a vitrification solution containing 6 mol ethylene glycol l(-1) and 0.3 mol raffinose l(-1) for 0.5, 1.0 or 2.0 min before vitrification. The vitrified and fresh preantral follicles were treated with collagenase, and the oocyte-granulosa cell complexes (OGCs) obtained were cultured in vitro for 10 days in membrane inserts. Preantral follicles exposed to 2 mol ethylene glycol l(-1) for 5 min and then to the vitrification solution for 0.5 or 1.0 min showed the highest survival rates after warming. The follicular loss after warming was approximately 20%. After in vitro culture, the proportion of viable OGCs from the vitrified follicles was 10% lower than that of the fresh preantral follicles. There were no differences in the rates of maturation, fertilization and subsequent development to blastocysts between the oocytes derived from vitrified follicles and those derived from fresh preantral follicles; however, the developmental competence of the oocytes derived from both vitrified and fresh preantral follicles grown in vitro was lower than that of oocytes grown in vivo. One of the five recipient mice that received 20 blastocysts derived from vitrified preantral follicles gave birth to six live pups. The results of the present study demonstrate for the first time that mouse preantral follicles can be vitrified and that some of the embryos derived from vitrified preantral follicles can develop to live pups.
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PMID:Birth of pups after transfer of mouse embryos derived from vitrified preantral follicles. 1191 21

We have developed synthetic hydrogel extracellular matrix (ECM) analogues that can be used to study mechanisms involved in cell migration, such as receptor-ligand interactions and proteolysis. The biomimetic hydrogels consist of bioinert polyethylene glycol diacrylate derivatives with proteolytically degradable peptide sequences included in the backbone of the polymer and adhesive peptide sequences grafted to the network. Hydrogels have been developed that degrade as cells secrete proteolytic enzymes. Adhesive peptide sequences grafted to the hydrogel provide ligands that can interact with receptors on the cell surface to mediate adhesion and spreading. In this study, we have characterized the effects of adhesive ligand density on fibroblast migration through collagenase-degradable and plasmin-degradable hydrogels and on smooth muscle cell migration through elastase-degradable hydrogels. In all three cases, we found that cell migration has a biphasic dependence on adhesion ligand concentration, with optimal migration at intermediate ligand levels. Furthermore, both adhesive and proteolytically degradable sequences were required for cell migration to occur. These synthetic ECM analogues may be useful for 3-D mechanistic studies of many aspects of cell migration
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PMID:Cell migration through defined, synthetic ECM analogs. 1192 20

Oxidation of proteins occurs both as a side-effect of aerobic energy metabolism and as an effect of specific metabolism of phagocytic polymorphonuclear granulocytes producing O2- and H2O2. In contrast to other cells, which control their H2O2 level by degrading it to O2 and H2O, polymorphonuclear neutrophilic leukocytes (PMN) use H2O2 as a substrate for oxidizing chloride ions to HOCl which rapidly react with all neighboring thiol, disulfide and amino residues. Chloramines, which are the most abundant HOCl reaction products, react with proteins, modifying only certain exposed methionine and cysteine residues. This may account for selective inactivation of a number of enzymes, carrier proteins and peptide mediators, including the alpha1-proteinase inhibitor, alpha2-macroglobulin and plasminogen activator inhibitor. Inactivaton of plasma proteinase inhibitors protects PMN elastase, collagenase, cathepsin G and other serine proteases in the inflammatory foci. This promotes proteolytic degradation of damaged tissue, removal of bacterial debris and wound healing, as well as tissue remodeling related to the inflammatory processes. Oxidative control of protease-anti-protease balance affects the development of the inflammatory processes. Moreover, inactivation of plasma proteinase inhibitors facilitates primary antigen processing, upregulates lymphocyte proliferative response and activates the local immune response. Oxidation produces a specific protein tagging which attracts and stimulates immune active cells. Therefore, humoral response against oxidatively modified proteins occurs more effectively than that of the native proteins. The effect is dose-dependent with respect to the amount of oxidant employed. Glycol aldehyde, which is the serine chloramine spontaneous decay product, in mice immunized with glycol aldehyde-modified egg-white albumin, yields specific IgG production manifold higher than that in mice immunized with native albumin. Immunopotentiation is produced by proliferation expansion of the same immunocompetent clones. Oxidative tagging of proteins may also affect the autoimmune-type reaction. Thus, a growing body of data suggest that the specific role of protein oxidation by activated PMN is oxidative protein tagging facilitating further development of the immune reaction.
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PMID:Myeloperoxidase-mediated protein oxidation: its possible biological functions. 1211 89

In this study a detailed description of the equine hepatocyte isolation procedure is presented. Livers were obtained from horses slaughtered at the local slaughterhouse. For blood removal and liver preservation the following steps are suggested: perfusion with the oxygenated HBSS (0-2 degrees C, with continuous flow of 500-800 ml/min for 3-6 min), protection from ischemia injury by flushing with ice-cold University of Wisconsin Solution (UW, flow rate of 500-800 ml/min), and finally immersion of the liver lobe in UW solution (2 degrees C) during its transport to the laboratory. For equine isolated hepatocyte preparation a "three-step" perfusion procedure was elaborated: rewarming, chelating and collagenase perfusion. We found optimal cell yield and viability under the following conditions: rewarming with UW (38 degrees C) for 8-14 min, chelating with calcium free Hanks' Balanced Salt Solution (HBSS, 38 degrees C) supplemented with 1 mM ethylene glycol-bis[beta-aminoethyl esther]-N,N,N'N'-tetracetic acid at the flow rate of 450 ml/min for 6 min and enzymatic digestion with HBSS supplemented with 0.1% collagenase at 38 degrees C and 450 ml/min flow rate for 8-27 min. These conditions consistently generated cell harvests of 21 x 10(6)+/-4.86 cells/g of perfused liver tissue with viability of 82.7%+/-10.2.
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PMID:Preparation of equine isolated hepatocytes. 1459 53

We have previously reported on the development and use of synthetic hydrogel extracellular matrix (ECM) analogues that can be used to study the mechanisms of migration. These biomimetic hydrogels consist of bioinert poly(ethylene glycol) diacrylate derivatives with proteolytically degradable peptide sequences included in the backbone of the polymer and adhesion peptide sequences grafted into the network. Cells adhere to the hydrogel via interaction between the grafted adhesion ligands and receptors on the cell surface. The cells migrate through the three-dimensional system by secreting the appropriate proteolytic enzymes, which are involved in cell migration and are targeted to the peptide sequences incorporated in the backbone of the polymer. It was observed that cell migration has a biphasic dependence on adhesion ligand concentration, with optimal migration at intermediate ligand levels. In this study, we demonstrate that we can covalently attach epidermal growth factor (EGF) to PEG and graft them into the hydrogels. It was observed that EGF when tethered maintained mitogenic activity. It was also observed that fibroblast migration significantly increased in the presence of the grafted EGF through the collagenase-sensitive hydrogels. In addition, the increase in migration was found to be independent from the proliferative response of the cells. These synthetic ECM analogues allow one to systematically control identities and concentrations of biomolecules and are useful tools to study mechanisms of cell migration.
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PMID:Effects of epidermal growth factor on fibroblast migration through biomimetic hydrogels. 1465 56

This research demonstrates that controlled material degradation and transforming growth factor-beta1 (TGF-beta1) release can be achieved by encapsulation of TGF-beta1-loaded gelatin microparticles within the biodegradable polymer oligo(poly(ethylene glycol) fumarate) (OPF), so that these microparticles function as both a digestible porogen and a delivery vehicle. Release studies performed with non-encapsulated microparticles confirmed that at normal physiological pH, TGF-beta1 complexes with acidic gelatin, resulting in slow release rates. At pH 4.0, this complexation no longer persists, and TGF-beta1 release is enhanced. However, by encapsulating TGF-beta1-loaded microparticles in a network of OPF, release at either pH can be diffusionally controlled. For instance, after 28 days of incubation at pH 4.0, final cumulative release from non-encapsulated microparticles crosslinked in 10 and 40 mM glutaraldehyde (GA) was 75.4+/-1.6% and 76.6+/-1.1%, respectively. However, when either microparticle formulation was encapsulated in an OPF hydrogel (noted as OPF-10 mM and OPF-40 mM, respectively), these values were reduced to 44.7+/-14.6% and 47.4+/-4.7%. More interestingly, release studies, in conditions that model the expected collagenase concentration of injured cartilage, demonstrated that by altering the microparticle crosslinking extent and loading within OPF hydrogels, TGF-beta1 release, composite swelling, and polymer loss could be systematically altered. Composites encapsulating less crosslinked microparticles (OPF-10 mM) exhibited 100% release after only 18 days and were completely degraded by day 24 in collagenase-containing phosphate-buffered saline (PBS). Hydrogels encapsulating 40 mM GA microparticles did not exhibit 100% release or polymer loss until day 28. Hydrogels with no microparticle component demonstrated only 79.3+/-9.2% release and 89.2+/-3.4% polymer loss after 28 days in enzyme-containing PBS. Accordingly, these studies confirm that the rate of TGF-beta1 release and material degradation can be controlled by altering key parameters of these novel, in situ crosslinkable biomaterials, so that TGF-beta1 release and scaffold degradation may be tailored to optimize cartilage repair.
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PMID:Transforming growth factor-beta 1 release from oligo(poly(ethylene glycol) fumarate) hydrogels in conditions that model the cartilage wound healing environment. 1468 75

The physiological activity of hyaluronic acid (HA) polymers and oligomers makes it a promising material for a variety of applications. The development of HA-hydrogel scaffolds with improved mechanical stability against degradation and biochemical functionality may enhance their application to tissue engineering. In this report, a crosslinking strategy targeting the alcohol groups via a poly(ethylene glycol) diepoxide crosslinker was investigated for the generation of degradable HA hydrogels. To provide support for cell adhesion in vitro, collagen was incorporated into the HA solution prior to the crosslinking process. The hydrogels have a continuous exterior and a porous interior, with pore diameters ranging from 6 to 9 microm. HA and HA-collagen hydrogels degrade in the presence of hyaluronidase and collagenase enzymes, indicating that the chemical modification does not prevent biodegradation. Complete degradation of the hydrogels occurred within 14 days in hyaluronidase (100 U/ml) and 3 days in collagenase (66 U/ml). Pattern transfer was employed to introduce a surface topography onto the hydrogel, which was able to orient cell growth. Furthermore, the hydrogels could be functionalized with the biomolecule neutravidin by incorporation of biotin along the HA backbone. This biotinylation approach may allow attachment of bioactive molecules that are conjugated to avidin.
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PMID:Crosslinked hyaluronic acid hydrogels: a strategy to functionalize and pattern. 1527 10

The realization of three-dimensional (3D) degradable matrices which slowly release bio-active components represents a major challenge in the field of tissue engineering. In this paper we report on the usage of commercially available bifunctional agents for both the covalent coupling of proteins to and the cross-linking of collagen matrices. Proteins - horse radish peroxidase (HRP) was used as a model protein - were cross-linked with either a homobifunctional (disuccinimidyldisuccinatepolyethylene-glycol) or a heterobifunctional (N-hydroxysuccinimidylvinylsulfonepolyethyleneglycol) agent. In the case of the heterobifunctional cross-linking agent the collagen matrices were previously modified with succinimidylacetylthioacetate in order to introduce sulfhydryl groups. As compared with control experiments a 10-fold and 50-fold increase of immobilized proteins were achieved with the homobifunctional and heterobifunctional cross-linker resp. The HRP-PEG conjugates demonstrated a better long-term stability as compared to the non-treated HRP. The effects of the cross-linking agents and the thiolation reagent succinimidylacetylthio acetate on the in vitro degradation of the collagen matrices by collagenase were also investigated. In particular the reaction with succinimidylacetylthio acetate appears to offer interesting opportunities both for coupling active proteins and modulating the degradation times of collagen matrices.
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PMID:The use of bifunctional polyethyleneglycol derivatives for coupling of proteins to and cross-linking of collagen matrices. 1534 72


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