Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutral endopeptidase-24.11 (EC 3.4.24.11) (NEP) is a transmembrane metallo-endopeptidase that has been shown to be involved in the degradation of several mammalian neuropeptides, including enkephalins. The enzyme has recently been found to be specifically associated with the axonal and synaptic membranes of neurons in the globus pallidus of the pig brain. This result suggests that neurons must possess mechanisms for targeting NEP to particular membrane domains. Study of these mechanisms would greatly benefit from the existence of an established neuron-like cell line capable of expressing and targeting NEP to specific membrane domains. For this reason we have used a retroviral vector containing the cDNA for rabbit kidney NEP to express this enzyme in a mouse neuroblastoma cell line (Neuro2A). Labelling of the cell surface with an antibody coupled to colloidal gold particles and examination of the cells by electron microscopy revealed a non-uniform distribution of NEP at the surface of the cells, the protein being preferentially associated with the membrane of neurites compared with the cell body. This observation suggests that Neuro2A cells possess a mechanism for targeting NEP to specific domains of the plasma membrane. This cell line could thus constitute a good model for studying the mechanisms responsible for targeting this enzyme to specialized regions of the plasma membrane.
 ...
PMID:Recombinant neutral endopeptidase-24.11 expressed in mouse neuroblastoma cells is associated with neurite membranes. 233 3

The messenger RNA (mRNA) encoding enkephalinase (EC. 3.4.24.11; neutral endopeptidase) has been localized in rat brain by in situ hybridization using 35S- or 32P-labelled cRNA probes. Hybridization was observed only in few brain areas, and was particularly strong in the striatum, olfactory bulb and pontine nuclei. The enkephalinase protein was also localized in brain sections using a radiolabelled monoclonal antibody. While some brain regions contained both the mRNA and its translation product, others, including in particular the substantia nigra, were rich in enkephalinase but did not contain any detectable amount of enkephalinase mRNA. Enkephalinase mRNA-containing cells could be identified in regions containing neurons known to project to the substantia nigra. The discrepancy between the mRNA and the protein labelling is likely to reflect the fact that the mRNA is exclusively located within the soma of the cells while the translated protein may be found anywhere along the axonal processes.
 ...
PMID:Localization of enkephalinase mRNA in rat brain by in situ hybridization: comparison with immunohistochemical localization of the protein. 281 91

An ultrastructural study of endopeptidase-24.11 in the globus pallidus from the brain of a newborn pig is reported. The antigen was localized by an immunoperoxidase method using an affinity-purified polyclonal antibody in which staining was performed on thick vibratome sections prior to osmication and flat embedding. When areas selected by light microscopy for re-embedding were examined in the electron microscope a minority of the axonal membranes in the fields examined were observed to be immunostained for endopeptidase-24.11. These were unmyelinated fibres and the membrane staining included not only the length of an axon but also some boutons synapsing with dendrites. Positively staining dendritic and glial membranes were not observed. These results support the view that endopeptidase-24.11 may play a role in inactivating some neuropeptides after their release at the synapse.
 ...
PMID:Electronmicroscopic immunocytochemistry of pig brain shows that endopeptidase-24.11 is localized in neuronal membranes. 307 48

The content and distribution of cathepsin D, a lysosomal acidic endopeptidase, were determined by immunochemical methods in rat sciatic nerve near the site of a ligature or after exposure of animals to neurotoxins. In normal sciatic nerve, cathepsin D was localized predominantly in the perinuclear regions of Schwann cells. In ligated nerve, cathepsin D increased equally in both the proximal and distal nerve segments adjacent to the ligature. Although orthograde and retrograde axonal transport of cathepsin D may have contributed to this increase, immunocytochemical methods indicated that Schwann cells or other phagocytic cells accounted for the bulk of the increased cathepsin D content of nerve. Axonal function was nontraumatically altered by the administration of 2,5-hexanedione, acrylamide, B,B'-iminodipropionitrile or zinc pyridinethione. Exposure to any of these neurotoxins raised cathepsin D content throughout the sciatic nerve twofold or more, and greater amounts of immunoreactive cathepsin D in the cytoplasm of Schwann cells could be demonstrated immunocytochemically. These results indicate that changes in cathepsin D content of Schwann cells may be a reflection of their catabolic activity. The increased Schwann cell cathepsin D content in toxic axonopathies is further proof for an enhanced Schwann cell role as a phagocyte resulting from axonal injury.
 ...
PMID:Changes in sciatic nerve cathepsin D after ligation or exposure to neurotoxins. 618 44

The effect of SR 48692, a potent and selective non-peptide antagonist of the neurotensin receptor, was investigated on the retrograde axonal transport of neurotensin in the rat nigrostriatal dopamine pathway. When rats were injected in the striatum with (3-[125I]iodotyrosyl3)neurotensin, a substantial accumulation of radioactivity appeared in the ipsilateral substantia nigra 1.5 h after injection, and highest levels (336 +/- 23 dpm/mg of protein) were observed 2.5-3.5 h after the injection. The phenomenon required a pretreatment of the animals with thiorphan (30 micrograms) an inhibitor of endopeptidase. The amount of radioactivity accumulated (3.5 h) was found to be reduced (25%) by local (100 nM) or peripheral administration of SR 48692 (5, 10, 20 mg/kg, i.p.; 25%, 40%, 40%, respectively). Our results indicate that blockade of neurotensin receptors by a selective non-peptide receptor antagonist affects the retrograde axonal transport of the tridecapeptide, and further suggest the notion that this process involves neurotensin receptors.
 ...
PMID:Blockade of neurotensin receptors by the antagonist SR 48692 partially prevents retrograde axonal transport of neurotensin in rat nigrostriatal system. 751 73

Endopeptidase-24.11, which is identical with the common acute lymphoblastic leukaemia antigen CD10 (CALLA), is a cell surface Zn2+ metalloprotease that regulates peptide-induced responses in different tissues, including the nervous and immune systems. In the peripheral nervous system, high levels of the enzyme are present in all neonatal and early postnatal Schwann cells, while as myelination proceeds it is gradually suppressed in the majority of cells that form myelin but retained in non-myelin-forming cells in the adult animal. In the present study we have investigated the effects of transection, crush and regeneration of the adult rat sciatic nerve on the expression of the endopeptidase by Schwann cells in situ. Endopeptidase-24.11 was monitored by immunocytochemistry using the monoclonal anti-endopeptidase antibody 23B11. For comparison, a parallel study was carried out with a monoclonal antibody directed against the rat nerve growth factor receptor. We found that (i) all Schwann cells of the distal segment re-expressed endopeptidase-24.11 as early as 4 days after axotomy, the level of immunostaining reaching a maximum after 2 weeks, (ii) axonal regeneration repressed Schwann cell expression of endopeptidase-24.11, and (iii) the induction of the nerve growth factor receptor followed a similar pattern to that of endopeptidase-24.11 in the transected and crushed nerve. Enzymatic amplification of endopeptidase-24.11 cDNA from normal and axotomized adult rat sciatic nerve confirmed the expression of endopeptidase-24.11 in these tissues. Our results show that the expression of endopeptidase-24.11 in Schwann cells, as is the case with the nerve growth factor receptor, is induced by the loss of the normal axon-Schwann cell contact. The significant increase in the expression of endopeptidase-24.11 by Schwann cells after axonal damage suggests that the enzyme could play a role in axonal regeneration.
 ...
PMID:Expression of endopeptidase-24.11 (common acute lymphoblastic leukaemia antigen CD10) in the sciatic nerve of the adult rat after lesion and during regeneration. 761 30

1. Cigarette smoke induces plasma exudation in the airways of rodents by activation of capsaicin-sensitive 'sensory-efferent' nerves. The response is mediated predominantly by substance P (SP) and the magnitude of exudation is regulated by neutral endopeptidase (NEP). The component(s) of the smoke responsible for the activation of the nerves may be reactive oxygen radicals. We investigated the effect of the hydroxyl radical scavenger dimethylthiourea (DMTU), a regulator of superoxide anion, superoxide dismutase (SOD), and a regulator of hydrogen peroxide, catalase, on plasma exudation (measured using Evans blue dye) induced by cigarette smoke in guinea-pig main bronchi in vivo. The effect of DMTU on plasma exudation and non-cholinergic bronchoconstriction (measured as pulmonary insufflation pressure, PIP) induced by electrical stimulation of the vagus nerves was also assessed. Interaction between hydroxyl radicals and NEP was assessed with the NEP inhibitor phosphoramidon. 2. In each of the experiments, cigarette smoke increased plasma exudation by approximately 200% above air-exposed controls. Acute administration of DMTU (1.5 g kg-1, i.v. for 20 min) significantly reduced cigarette smoke-induced plasma exudation by 69%. In contrast, neither SOD (240,000 u kg-1, i.v.) nor catalase (400,000 u kg-1, i.v.) significantly affected the exudative response. 3. Chronic pretreatment with DMTU (1.25 g kg-1 over 4 days) significantly reduced bronchial plasma exudation induced by cigarette smoke by 72%. Phosphoramidon (1.5 mg kg-1, i.v.) completely reversed the inhibition by DMTU of cigarette smoke-induced plasma exudation. 4. Vagal stimulation increased plasma exudation by approximately 200% and PIP by approximately 250%. Acute treatment with DMTU had no significant inhibitory effect on these responses, whereas chronic pretreatment inhibited them by approximately 80%. Phosphoramidon reversed the inhibition by chronic DMTU. 5. SP (1 nmol kg-1) increased plasma exudation by approximately 250%, a response which was not inhibited by either acute or chronic DMTU. 6. We conclude that hydroxyl radicals, rather than superoxide anion or hydrogen peroxide, are involved in the induction of neurogenic plasma exudation and bronchoconstriction induced by cigarette smoke or by electrical stimulation of the vagus nerves. These radicals also affect the activity of NEP. Acute DMTU may affect directly the neural actions of hydroxyl radicals contained in the cigarette smoke. Chronic pretreatment with DMTU may inhibit the neurogenic airway responses by effects on tachykinin biosynthesis and/or axonal transport.
 ...
PMID:Involvement of hydroxyl radicals in neurogenic airway plasma exudation and bronchoconstriction in guinea-pigs in vivo. 882 33

1. Sensory afferent fibres mediate important protective reflexes in the lung. Small, unmyelinated C-fibre nerves have both sensory afferent and effector functions. C-fibres contain a number of neuropeptides, including the tachykinins, which have pro-inflammatory effects in the airways. Following stimulation with capsaicin and other stimuli, neuropeptides are released from the nerve endings, either directly or by axonal reflexes. 2. Important tachykinin effects include smooth muscle contraction, vasodilatation and oedema, mucus secretion and inflammatory cell activation. There are also trophic effects, including proliferation of fibroblasts, smooth muscle and epithelial cells. 3. Tachykinins mediate their effects by binding to G-proteinlinked receptors. Receptor-specific agonists and antagonists are available, which have helped clarify the effects of tachykinins. These agents may have therapeutic potential. 4. Tachykinins are degraded by the enzyme neutral endo-peptidase. 5. Studies in humans in vivo show an increase in airways resistance following challenge with tachykinins. There is some evidence for an increase in tachykinins and their receptors in airway inflammation, but this has not been found in all studies. A reduction in neutral endopeptidase has been seen in some animal models of airway inflammation, but this has not been shown in human disease. 6. Trials of tachykinin receptor antagonists in human asthma have begun, but it is too early to say what their therapeutic impact will be.
 ...
PMID:Role of tachykinins in bronchial hyper-responsiveness. 913 Dec 97

Calcium activated neutral proteinase (calpain) is an endopeptidase present in the central nervous system which degrades myelin proteins. To examine the role of calpain in demyelination associated with optic neuritis, immunocytochemical expression of calpain was evaluated in Lewis rats with experimental optic neuritis. Calpain expression was increased in activated microglia, infiltrating macrophages, activated T cells, and reactive astrocytes in experimental optic neuritis compared to controls. Calpain activity and translational expression were also examined by Western blotting studies measuring the extent of myelin protein degradation, calpain-specific fodrin proteolysis, axonal neurofilament degradation, and calpain proenzyme content. Results showed myelin associated glycoprotein and 68 kD neurofilament protein levels were significantly decreased while calpain translational expression and calpain-autolyzed fodrin levels were significantly increased in experimental optic neuritis compared to controls. Thus, increased activity and translational expression of calpain in optic neuritis may be integral to the pathogenesis of this disorder.
 ...
PMID:A putative role for calpain in demyelination associated with optic neuritis. 1021 25

Chronic constriction injury (CCI) to peripheral nerve causes a painful neuropathy in association with a process of axonal degeneration and endoneural remodeling that involves macrophage recruitment and local increase in extracellular proteases and tumor necrosis factor alpha (TNF-alpha). Cell surface activation of TNF-alpha from its transmembrane precursor, as well as sequestration of TNF-alpha receptors II and I, is performed by the zinc-dependent endopeptidase family of matrix metalloproteinases (MMPs). Among TNF-alpha-converting MMPs, basal lamina degrading gelatinases are thought to play a role in sciatic nerve injury. In the present study, we determined the forms of TNF-alpha involved in the development of CCI neuropathy in rats, using Western blot analysis, and the temporal correlation of TNF-alpha and TNFRI protein profiles with gelatinases activity at the site of peripheral nerve injury. We observed two peaks in TNF-alpha protein during the first week of CCI that correspond to previously reported peaks in painful behavior. We propose that the first peak at 6 h post-CCI is due to the local expression of the cytotoxic transmembrane 26 kDa TNF-alpha protein released by resident Schwann cells, mast cells and macrophages. This peak in TNF-alpha protein expression corresponds to an increase in gelatinase B (MMP-9) activity, which is greatly upregulated as early as 3 h following CCI to rat sciatic nerve. The second peak occurs at 5 days post-CCI, and may represent TNF-alpha protein released by hematogenously recruited macrophages. This peak is marked by the increase in active soluble 17 kDa TNF-alpha and by gelatinase A (MMP-2) upregulation. These observations suggest that there is a pathogenic role for the TNF-alpha-converting function of MMP-2 in painful CCI neuropathy. We conclude that severe nerve injury induces MMPs, TNF-alpha and TNFRI, which interactively control the privileged endoneurial environment and the pathogenesis of the painful neuropathies associated with the macrophage-dependent processes of Wallerian degeneration.
 ...
PMID:Upregulation and interaction of TNFalpha and gelatinases A and B in painful peripheral nerve injury. 1065 Jan 33


1 2 3 Next >>