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)

Matrix metalloproteinases (MMPs) comprise a family of proteolytic enzymes that are involved in remodeling of the extracellular matrix (ECM) of many tissues. They have been implicated in degradation of vascular basement membranes thereby facilitating leukocyte migration into inflammatory sites. To determine the cellular localization and levels of MMPs in the normal human central nervous system (CNS), multiple sclerosis (MS) lesions, and other conditions, cryostat sections of CNS samples were immunostained with antisera to MMP-1, -2, -3 and -9. In control white matter the principal cells that express the MMPs were perivascular and parenchymal microglia. Cellular MMP expression was also found in sporadic microglial nodules in MS white matter. Most CNS microvessel endothelial cells expressed MMP-3 and -9 but not MMP-1 or -2. The majority of macrophages in active MS and necrotic lesions were MMP-l-, -2-, -3-, and -9-positive whereas chronic MS lesions had fewer MMP-positive macrophages. Small numbers of astrocytes were MMP-2-, -3- and -9-positive in acute and chronic MS lesions. These data suggest that microglia-derived MMPs may mediate turnover of the CNS ECM under normal conditions and in microglial nodules. In sites of CNS tissue injury there is complex and dynamic regulation of MMP expression by different cell populations. In MS lesions MMP-mediated proteolysis may contribute to breakdown of the blood-brain barrier and leukocyte migration into the CNS, in situ immune activation, demyelination, metabolism of bioactive peptides, and the formation of an ECM that does not promote remyelination or axonal repair.
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PMID:Matrix metalloproteinases in the normal human central nervous system, microglial nodules, and multiple sclerosis lesions. 878 88

The distribution and biochemical features of the synapsin-like peptides recognized in Aplysia and Helix by various antibodies directed against mammalian synapsins were studied. The peptides can be extracted at low pH and are digested by collagenase; further, they can be phosphorylated by both protein kinase A and Ca2+/calmodulin-dependent protein kinase II. In the ganglia of both snails, they are associated with the soma of most neurons and with the neuropil; punctate immunostaining is present along the neurites. Using cocultures of a Helix serotoninergic neuron and of its target cell, we analysed the redistribution of the synapsin-like peptides during the formation of active synaptic contacts. When the presynaptic neuron is plated in isolation, both synapsin and serotonin immunoreactivities are restricted to the distal axonal segments and to the growth cones; in the presence of the target, the formation of a chemical connection is accompanied by redistribution of the synapsin and serotonin immunoreactivities that concentrate in highly fluorescent round spots scattered along the newly grown neurites located close to the target cell. Almost every spot that is stained for serotonin is also positive for synapsin. In the presynaptic cell plated alone, the number of these varicosity-like structures is substantially stable throughout the whole period; by contrast, when the presynaptic cell synapses the target, their number increases progressively parallel to the increase in the mean amplitude of cumulative excitatory postsynaptic potentials recorded at the same times. The data indicate that mollusc synapsin-like peptides to some extent resemble their mammalian homologues, although they are not exclusively localized in nerve terminals and their expression strongly correlates with the formation of active synaptic contacts.
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PMID:Synapsin-like molecules in Aplysia punctata and Helix pomatia: identification and distribution in the nervous system and during the formation of synaptic contacts in vitro. 899 2

We studied the expression of candidate molecules for tissue injury in vasculitic neuropathies immunohistochemically, using samples obtained by nerve biopsy from seven patients with necrotizing angitis. In the involved vessels of all samples, numerous infiltrating cells were positive for perforin, nitric oxide synthase (m-NOS), cyclooxygenase-2 (COX-2), or matrix metalloproteinase-1 (MMP-1). Cell-mediated cytotoxicity may be involved in the pathogenesis of small vessel injury in vasculitic neuropathies. In the endoneurium following axonal degeneration, scattered and phagocytosing macrophages showed immunostaining for m-NOS and MMP-1, but COX-2 was all but restricted to phagocytosing macrophages. This suggests a role for prostaglandins in nerve damage.
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PMID:Mechanisms of tissue injury in vasculitic neuropathies. 948 78

A method for patch-clamp recording from intact dorsal root ganglion (DRG) cells in rat is described. The L4 and L5 DRGs with sciatic nerve attached were excised from rats (10-15 days old) and placed in a recording chamber after removing the ganglion sheath and dissolving the connective tissue with dilute collagenase. The somata of individual cells were exposed by gentle surface cleaning through a perfusion micropipette. Somata were classified as Abeta, Adelta or C based on the cell size and the shape of the action potential (AP). Under current clamp, axonal conduction velocity (CV) was calculated from the distance between a stimulating electrode and the center of the ganglion divided by the latency of the AP elicited by stimulation of the sciatic nerve. CVs ranged from 0.2-0.8 m/s for C cells, 0.8-2.4 for Adelta and 3.2-5.0 for A/beta cells. AP threshold occurred at a significantly more positive potential in C cells than in Adelta and Abeta cells. Under voltage clamp, sodium currents were recorded from C cells. Both TTX-resistant (TTX-R) and TTX-sensitive (TTX-S currents) were demonstrated in the present study. The results demonstrate the feasibility of patch-clamp recording from intact, identified DRG cells in vitro.
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PMID:Patch clamp recording from the intact dorsal root ganglion. 953 65

Bacterial collagenase was injected into the vitreous of the eye of chick and quail embryos. Immunocytochemical and ultrastructural studies revealed that the collagenase dissolved the retinal basal lamina of the injected eye. The basal lamina disruption was first detectable 1 hour after enzyme injection and was complete within 3 hours. With further development, the retinal basal lamina was not reestablished; newly developing neuroepithelium in the peripheral retina, however, generated an intact basal lamina. Western blot analysis showed that Clostridial collagenase degraded various collagens but spared noncollagenous proteins. Basal lamina disruption of embryonic day 3 to 6 retinae led to the retraction of the end feet of the neuroepithelial cells, caused an increase in the number of Islet-1+ cells (most likely ganglion cells), an increase in the thickness of the optic fiber layer, and aberrant growth of optic axons on their way toward the optic disc. None of these changes were observed when retinal basal laminae were disrupted at later stages of development. The present data demonstrate that the retinal basal lamina, by anchoring the neuroepithelial cells to the pial surface of the retina, has an important function in the development of the normal cytoarchitecture of this structure. It is proposed that the altered extracellular environment in the vitreal part of the retina, resulting in the retraction of the neuroepithelial end feet, is responsible for the increased number of Islet-1+ cells and the aberrant axonal navigation.
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PMID:Disruption of the retinal basal lamina during early embryonic development leads to a retraction of vitreal end feet, an increased number of ganglion cells, and aberrant axonal outgrowth. 967 Dec 81

Bacterial collagenase was injected into the ventricular cavity of the optic tectum of chick and quail embryos. Histological examination up to 6 days after enzyme injection revealed that the collagenase disrupted the pial basal lamina, which was evident by the fragmented distribution of basal lamina proteins at the pial surface of the midbrain and the brainstem. Although the disrupted basal lamina was not reestablished at later stages of development, the pial basal lamina of the newly developing neuroepithelium in the caudal part of the tectum was continuous and intact. Western blot analysis showed that the collagenase digested collagens but spared noncollagenous proteins. The disruption of the pial basal lamina caused the neuroepithelial cells to retract their pial end feet and caused tectal axons to exit the brain tissue into the adjacent mesenchyme. The vertical migration of neuroblasts to the pial layers of the tectum was inhibited, leading to a disruption of the tectal histogenesis. In the developing optic pathways, retinal axons were misguided at the optic chiasma and terminated in the head mesenchyme instead of the tectum. None of the abnormalities in histogenesis and axonal pathways were observed when the basal lamina was disrupted at a later stage of embryonic development. The present experiments demonstrate that the pial basal lamina has an important function during brain morphogenesis in restricting axons to the brain, providing an anchoring of the neuroepithelial cells to the pial surface, and allowing the formation of a defined cytoarchitecture of the brain.
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PMID:Disruption of the pial basal lamina during early avian embryonic development inhibits histogenesis and axonal pathfinding in the optic tectum. 967 Dec 82

In urodele amphibian spinal cord regeneration, the ependymal cells lining the central canal remodel the lesion site to favor axonal regrowth. We profiled the production of matrix metalloproteinases by injury-reactive mesenchymal ependymal cells in vivo and in vitro and found that matrix metalloproteinases are involved in this remodeling process in the axolotl (Ambystoma mexicanum). The production of cell-associated matrix metalloproteinases in vivo was shown to be identical to that in our cultured ependymal cell model system. Activated and zymogen forms of matrix metalloproteinases were identified using zymography, chemical inhibitors of matrix metalloproteinases, and cleavage of propeptides by organomercurials. The principal cellular proteinases consisted of matrix metalloproteinase-2 (gelatinase A) and matrix metalloproteinase-1 (type I collagenase), which display characteristic shifts in molecular weight following proenzyme processing by organomercurials. In addition, ependymal cell conditioned medium contained secreted forms of the enzyme undetectable in situ. Matrix metalloproteinase-9 (gelatinase B) as well as matrix metalloproteinase-2 and matrix metalloproteinase-1 were secreted and casein substrate zymography showed the presence of a small amount of a very high molecular weight matrix metalloproteinase-3 (prostromelysin) secreted into the culture medium. Matrix metalloproteinases were still present at 4 weeks post-lesioning when the ependymal cells have just re-epithelialized, but decreased near the completion of regeneration (8 weeks post-lesioning). Zymography showed no detectable matrix metalloproteinases in unlesioned cord but the presence of tissue inhibitor of metalloproteinase-1 in intact cord was seen by Western blotting. This study shows that matrix metalloproteinases are associated with urodele spinal cord regeneration and validates the use of our ependymal cell tissue culture model system to evaluate ependymal cell behavior during spinal cord regeneration.
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PMID:Matrix metalloproteinase production in regenerating axolotl spinal cord. 1101 20

Matrix metalloproteinases (MMPs) are endoproteases that have been implicated in the pathogenesis of inflammatory and vasculitic neuropathies. In systemic lupus erythematosus (SLE), a peripheral neuropathy is frequently seen that is thought to be caused by ischemic nerve damage due to vasculopathy and/or vasculitis of the nutritional vessels. However, the exact pathomechanisms causing SLE neuropathy are largely unknown. Elevated MMP levels have been reported in the serum of SLE patients. Supposing that altered expression of MMPs may contribute to vessel wall damage in SLE neuropathy, we investigated the expression of MMP-1, -2, -3, -9, -10 and -13, and their tissue inhibitors (TIMP-1 and -2) in sural nerves from 12 SLE patients in comparison to normal controls. All MMPs could be detected within blood vessel walls from SLE nerves, whereas in controls MMP-3 and MMP-9 was not found. TIMP-1 and TIMP-2, on the other hand, were not informative. Generally, small and large nutritional vessels in the epineurium were immunoreactive for MMPs and TIMPs. Mononuclear cells, which expressed MMP-1, - 3, -10, -13, and TIMP-1 were also observed in most of the SLE nerves, mostly around epineurial blood vessels, but only occasionally in controls. This indicates that expression of MMPs in mononuclear cells may be related to leukocyte trafficking through the vessel walls. However, the density of TIMP-positive and MMP-positive inflammatory cells did not correlate with morphometric parameters regarding the severity of the neuropathy. Our findings suggest that especially the up-regulation of MMP-3 and MMP-9 within the vessel walls may be responsible for the vascular damage seen in SLE and the resulting chronic combined axonal and demyelinating type of neuropathy frequently found in SLE.
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PMID:Peripheral neuropathy in systemic lupus erythematosus: pathomorphological features and distribution pattern of matrix metalloproteinases. 1262 90

Confocal analysis of the whole-mount rat mesenteric branch arteries (MBA) revealed nucleated structures with axonal processes which immunostained for calcitonin gene-related peptide (CGRP). Immunocytochemistry ruled out the possibility that these were immune elements (macrophages and mast or dendritic cells) in close proximity with nerve fibers. To test our hypothesis that beta-CGRP is expressed in the rat MBA, we performed RT-PCR using total RNA isolated from the mesenteric artery arcade and intron spanning primers designed to amplify 188 bp of the beta-CGRP and 333 bp of alpha-CGRP cDNA. The PCR yielded an amplicon of the predicted size which was cloned into the pCR 3.1 vector. DNA sequence analysis of the insert showed 100% homology with the beta-CGRP cDNA, indicating that mRNA encoding beta-CGRP is expressed in the vessel. To learn whether neuronal cell bodies are located in the adventitia of MBA, we performed a limited collagenase digestion of isolated segments and plated the resulting cells in Ham's F12 medium with 10% horse serum on polyornithine-coated cover glasses. The medium was replaced after 48 h with Ham's F12 nutrient mixture containing N2 supplement. This resulted in a mixed population of fibroblasts, a small number of smooth muscle cells and a subset of cells that sprouted axons and immunostained positively for neuronal cell adhesion molecule and CGRP antigens. Fibroblasts and smooth muscle cells did not label with these antibodies. These data demonstrate, for the first time, that a population of adventitial neuronal somata (termed ANNIES), possibly of sensory nerve origin, is located in small mesenteric arteries.
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PMID:Adventitial neuronal somata. 1663 76

Derivative myelin associated glycoprotein (dMAG) results from proteolysis of transmembrane MAG and can inhibit axonal growth. We have tested the ability of certain matrix metalloproteinases (MMPs) elevated with inflammatory and demyelinating diseases to cleave MAG. We show MMP-2, MMP-7 and MMP-9, but not MMP-1, cleave recombinant human MAG. Cleavage by MMP-7 occurs at Leu 509, just distal to the transmembrane domain and, to a lesser extent, at Met 234. We also show that MMP-7 cleaves MAG expressed on the external surface of CHO cells, releasing fragments that accumulate in the medium over periods of up to 48 h or more and that are able to inhibit outgrowth by dorsal root ganglion (DRG) neurons. We conclude that MMPs may have the potential both to disrupt MAG dependent axon-glia communication and to generate bioactive fragments that can inhibit neurite growth.
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PMID:Cleavage of myelin associated glycoprotein by matrix metalloproteinases. 1806 13


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