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

Endopeptidase-24.11 (neutral endopeptidase, neprilysin, 'enkephalinase', EC 3.4.24.11) and endopeptidase-24.18 (endopeptidase-2, meprin, EC 3.4.24.18) are cell-surface zinc-dependent metallo-endopeptidases able to cleave a variety of bioactive peptides including growth factors. We report the first study of the cellular and tissue distribution of both enzymes and of the mRNA for NEP during embryonic development in the rat. Endopeptidase-24.11 protein was first detected at E10 in the lining of the gut and, at E12, the enzyme was present on the notochord, medial and lateral nasal processes, otocyst, mesonephros, heart and neuroepithelium. In contrast, at this time endopeptidase-24.18 was present only on the apical surface of the neuroepithelial cells. By E14 and E16, NEP was also detected in a wide range of craniofacial structures, notably the palatal mesenchyme, the choroid plexus, tongue and perichondrium. The distribution of endopeptidase-24.18 at these stages was restricted to the inner ear, the nasal conchae, and ependymal layer of the brain ventricles and the choroid plexus. Although endopeptidase-24.11 had been detectable in the craniofacial vasculature at E12 and E14, this was no longer apparent at E16. Significantly, the distribution of endopeptidase-24.11 mRNA closely matched the immunolocalization of the protein at all stages investigated. In order to explore the functional role of these enzymes, inhibition studies were carried out using two selective inhibitors of endopeptidase-24.11, phosphoramidon and thiorphan. E9.5 and E10.5 embryos exposed to either inhibitor displayed a characteristic, asymmetric abnormality consisting of a spherical swelling, possibly associated with a haematoma, predominantly on the left side of the prosencephalon, and the severity of this defect appeared to be a dose-dependent phenomenon. This study suggests that these enzymes play previously unrecognized roles during mammalian embryonic development.
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PMID:Distribution of, and a putative role for, the cell-surface neutral metallo-endopeptidases during mammalian craniofacial development. 772 May 64

Multipotent neural stem cells (NSCs) present in the developing neural tube (E10.5, neuroepithelial cells; NEP) were examined for the expression of candidate stem cell markers, and the expression of these markers was compared with later appearing precursor cells (E14.5) that can be distinguished by the expression of embryonic neural cell adhesion molecule (E-NCAM) and A2B5. NEP cells possess gap junctions, express connexins, and appear to lack long cilia. Most candidate markers, including Nestin, Presenilin, Notch, and Numb, were expressed by both NEP cells as well as other cell populations. Fibroblast growth factor receptor 4 (FGFR4), Frizzled 9 (Fz9), and SRY box-containing gene 2 (Sox2) as assessed by immunocytochemistry and in situ hybridization are markers that appear to distinguish NSCs from other precursor cells. Neither Hoechst 33342 nor rhodamine-123 staining, telomerase (Tert) expression, telomerase activity, or breakpoint cluster region protein 1 (Bcrp1) transporter expression could be used to distinguish NEP stem cells from other dividing cells. NEP cells, however, lacked expression of several lineage markers that are expressed by later appearing cells. These included absence of expression of CD44, E-NCAM, A2B5, epidermal growth factor receptor (EGFR), and platelet-derived growth factor receptor-alpha (PDGFR alpha), suggesting that negative selection using cell surface epitopes could be used to isolate stem cell populations from mixed cultures of cells. Using mixed cultures of cells isolated from E14.5 stage embryos, we show that NEP cells can be enriched by depleting differentiating cells that express E-NCAM or A2B5 immunoreactivity. Overall, our results show that a spectrum of markers used in combination can reliably distinguish multipotent NSCs from other precursor cells as well as differentiated cells present in the CNS.
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PMID:Properties of a fetal multipotent neural stem cell (NEP cell). 1243 54

In old male Wistar rats (older than 12 months), or adult males (3-4 months) subjected to prenatal hypoxia (7% 02, 3 h, E14), a disruption of short-term memory was observed. The prenatal hypoxia also led to a decrease in the brain cortex expression of metallopeptidases neprilysin (NEP) and endothelin-converting enzyme (ECE-1) which regulate some neuropeptides and are the main beta-amyloid-degrading enzymes. Moreover, a significant decrease (by 2.7 times) in NEP activity in the sensorimotor cortex of old and adult rats subjected to prenatal hypoxia (by 1.7 times) was observed. To confirm possible involvement of these enzymes in memory, the analysis of the effect of microinjections of phosphoramidon (an inhibitor of NEP and ECE-1), and thiorphan (an inhibitor of NEP) into the rat sensorimotor cortex was carried out. In a two-level radial maze test, a disruption of short-term memory was observed 60 and 120 min after i.c. injection ofphosphoramidon (5.9 microg/microl) and 30 and 60 min after i.c. injection of thiorphan (2.5 microg/microl). The involvement of NEP and ECE-1 in short-term memory suggests that a decrease in the level of expression and activity of metallopeptidases involved in metabolism of beta-amyloid peptide (Abeta) and other neuropeptides is one of the main factors in disruption of cognitive functions after prenatal hypoxia or in the process of ageing.
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PMID:[Changes in the activity of amyloid-degrading metallopeptidases leads to disruption of memory in rats]. 1994 40

Endothelin-converting enzyme-1 (ECE-1) is a membrane-bound metalloprotease that cleaves biologically inactive big endothelin-1 (ET-1) into active ET-1. ET-1 is involved in the cardiovascular homeostasis and the development of cardiovascular diseases including pulmonary arterial hypertension and heart failure. Atrial natriuretic peptide (ANP) is an endogenous hormone that is released from the heart in response to myocardial stretch and overload. ANP was shown to be hydrolyzed by neutral endopeptidase 24.11 (NEP) which shares important structural features with ECE-1. Previous in vitro studies using recombinant soluble ECE-1 suggested that ECE-1 cleaved several biologically active peptides including ANP in addition to big ET-1. However, physiological relevance of ANP-degrading activity by ECE-1 has stayed unclear. Here, we aimed to investigate whether endogenous ECE-1 is able to hydrolyze ANP using live-cell based assay and ECE-1-deficient mice. Chinese hamster ovary (CHO) cells, which lack detectable levels of ECE activity, degraded ANP in the medium efficiently when transfected with ECE-1 cDNA. ANP peptide contents in the E14-15 embryos were significantly higher in ECE-1+/- mice compared with ECE-1+/+ mice. These observations strongly suggest that ECE-1 is involved in the physiological degradation of ANP in vivo. Thus, pharmacological inhibition of ECE-1 may provide a novel strategy to treat various cardiovascular diseases by suppressing and potentiating the ET and ANP pathway, respectively.
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PMID:Physiological relevance of hydrolysis of atrial natriuretic peptide by endothelin-converting enzyme-1. 2297 25

Analysis of the effect of a caspase-3 inhibitor on the content of the amyloid-degrading neuropeptidase neprilysin (NEP) in the cortex of rats subjected to prenatal hypoxia (7% O2, 3 h) on the 14-th day of the embryonic development (E14) was performed. It was found that rats subjected to prenatal hypoxia on days 20-30 after birth have an increased content and activity of caspase-3 with reduced levels of NEP and of the C-terminal fragment of the amyloid precursor protein (AICD) regulating NEP expression. In hypoxic animals 3 days after a single injection of a caspase inhibitor (i. v., Ac-DEVD-CHO, P20) the content of AICD and NEP was found to be increased up to the levels observed in control rats. The data obtained suggest that the increase of caspase-3 enzyme activity could affect NEP expression via proteolytic degradation of its transcription factor AICD. These data for the first time demonstrate the role of caspases in AICD-dependent regulation of NEP production in the brain of mammals under hypoxic conditions.
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PMID:[ROLE OF CASPASE-3 IN REGULATION OF THE CONTENT OF THE AMYLOID-DEGRADING NEUROPEPTIDASE NEPRILYSIN IN THE CORTEX OF RATS AFTER HYPOXIA]. 2698 77