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)

The purpose of this study was to identify the presence of placental neutral metalloendopeptidase (NEP; enkephalinase; EC 3.4.24.11) in human normotensive and pre-eclamptic pregnancy. The localization of NEP in placentae from normotensive, chronic hypertensive and pre-eclamptic pregnancies was carried out on fresh frozen tissues by using a monoclonal primary antibody developed against human common acute lymphoblastic leukaemia antigen (CD10) together with the avidin-biotin-peroxidase method. In placentae from normotensive, chronic hypertensive and superimposed pre-eclamptic pregnancies, intense staining was found in the extravillous trophoblast, and also in fibroblasts of the chorionic plate and stem villi. Light to moderate staining was noted in the villous-associated trophoblast and in some cells from the villous core. In cases of pre-eclampsia, very intense staining was detected not only on the surface, but also in the cytoplasm of the villous-associated trophoblast. The increased expression of placental NEP in pre-eclampsia suggests that this enzyme may be involved in the regulation of the local concentration of circulating biologically active peptides at the fetomaternal interface, and thus could be implicated in the pathophysiological changes of this syndrome.
Placenta 1995 Jul
PMID:Increased immunohistochemical expression of neutral metalloendopeptidase (enkephalinase; EC 3.4.24.11) in villi of the human placenta with pre-eclampsia. 747 14

Neutral endopeptidase (NEP)/CD10, a cell-surface peptidase degrading various bioactive peptides, is mainly present in syncytiotrophoblasts in the human placenta. However, the change in NEP expression upon trophoblast differentiation remains to be clarified. In the present study, we examined the expression of NEP in the differentiating trophoblast using the BeWo choriocarcinoma cell line as a model system. Under the normal culture conditions, NEP was very weakly expressed on most proliferating cytotrophoblastic BeWo cells, while a minority of the cell population (less than 5 per cent ), consisting of giant, multinucleated cells, clearly expressed NEP at the cell membrane. Treatment of BeWo cells with forskolin (FSK) for 48-72 h resulted in an 11- to 44-fold increase in the level of hCG secretion and induced cell fusion leading to the formation of multinucleated syncytiotrophoblasts, indicating functional and morphological differentiation. Fluorescence-activated cell sorting (FACS) analysis revealed that treatment with FSK significantly increased the cell-surface protein expression of NEP on differentiating BeWo cells. Consistently, there was a significant increase in the NEP enzymatic activity after FSK treatment. The level of hCG secretion from the FSK-treated cells was further enhanced when the cells were treated in the presence of the NEP inhibitor phosphoramidon. Immunohistochemical analysis of normal chorionic villi and choriocarcinoma tissues revealed the localization of NEP in syncytiotrophoblastic cells, as opposed to weak or negative staining in cytotrophoblastic cells. These data demonstrate that induction of choriocarcinoma cell differentiation is associated with an increase of NEP/CD10 expression at the cell surface, suggesting a role of this enzyme in regulating differentiated trophoblast functions such as hCG secretion. NEP/CD10 may also be a new cellular differentiation marker of both the normal and neoplastic trophoblast.
Placenta 2001 Jul
PMID:Upregulation of neutral endopeptidase expression and enzymatic activity during the differentiation of human choriocarcinoma cells. 1144 May 42

Neutral endopeptidase 24.11 (NEP) is identical to CD10, which is a differentiation antigen for early B-lymphoid progenitors in the B-cell differentiation pathway. This ectoenzyme is known to have a key role in the control of growth, differentiation, and signal transduction of many cellular systems by regulating bioactive peptides and cytokines. Recently, we demonstrated that NEP/CD10 is upregulated during forskolin-induced choriocarcinoma cell differentiation, suggesting that NEP/CD10 is a trophoblast differentiation marker. The purpose of this study was to clarify the enhancement of NEP/CD10 expression and its signal transduction pathway during phorbol ester (PMA)-induced differentiation of BeWo choriocarcinoma cells. PMA-induced differentiation of BeWo cells was confirmed by morphological change and human chorionic gonadotropin (hCG) secretion, which was completely blocked by a protein kinase C (PKC) inhibitor, Bisindolylmaleimide I (Bis I). On immunoblot analysis, PMA enhanced NEP/CD10 expression in a dose- and time-dependent manner, which was completely abolished by Bis I and a mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor, PD98059. PMA also induced phosphorylation of p44/p42 extracellular signal-regulated kinases (ERK) 1 and 2. These observations indicated that activation of PKC by PMA induced differentiation of BeWo cells, and that PMA activated MAPK/ERK, which resulted in the enhancement of NEP/CD10 expression. Furthermore, immunocytochemical analysis showed that NEP/CD10 expression was detected on the membranes of PMA-treated differentiated BeWo cells. In summary, we demonstrated that NEP/CD10 was enhanced during PMA-induced differentiation of BeWo choriocarcinoma cells through a PKC-dependent MEK/ERK signalling pathway. Our findings also suggest that NEP/CD10 may play a functional role in the process of trophoblast differentiation.
Placenta 2002 Jul
PMID:Neutral endopeptidase/CD10 expression during phorbol ester-induced differentiation of choriocarcinoma cells through the protein kinase C- and extracellular signal-regulated kinase-dependent signalling pathway. 1213 45

The presence of an extrahypothalamic gonadotropin releasing hormone (GnRH) in human placenta is well known and this decapeptide is presumed to play an important role in the regulation of the function and growth of human placenta. Immunohistochemistry showed that neutral endopeptidase 24.11 (NEP), a candidate of the responsible enzyme of GnRH degradation, is highly expressed on the cell surface of trophoblasts. Hydrolysis of GnRH by human villi was studied by measuring liberated amino acids using high performance liquid chromatography. The GnRH degrading activity was 1.53 times higher after incubation with the membrane fraction of first trimester villi than that after incubation with the membrane fraction of term villi. Phosphoramidon, a potent inhibitor of NEP, reduced the liberated amino acids to about a half, suggesting that NEP is a responsible enzyme for GnRH degradation. Ubenimex, which can inhibit several aminopeptidases, also reduced the liberated amino acids to about 50 per cent. O-phenanthroline, EDTA, and thiorphan could inhibit GnRH degradation but inhibitors of post proline endopeptidase could not. Furthermore, GnRH degrading activity of the membrane fraction was reduced remarkably after the membrane fraction was immunotitrated by anti NEP and anti placental leucine aminopeptidase (P-LAP) IgG. In conclusion, NEP and P-LAP are responsible enzymes for GnRH degradation in human villi.
Placenta 2002 Jul
PMID:Possible involvement of placental peptidases that degrade gonadotropin-releasing hormone (GnRH) in the dynamic pattern of placental hCG secretion via GnRH degradation. 1213 46

Chorioangiomas are benign angiomatous tumours of the placenta occurring with a frequency of approximately one per cent of all examined placentae. Hypoxia and genetic factors are discussed to be predisposing factors for chorioangiomas. However, not much is known about the tumorigenesis of these benign tumours. Screening with various antibodies in a rare case of chorangiomatosis, we found disseminated spindle cells coexpressing vascular epithelial growth factor (VEGF), neutral endopeptidase 24.11 (NEP/CD10), and KIT protein (CD117) within the tumour stroma. A possible involvement of such factors in angiogenesis and tumorigenesis of chorioangiomas/chorangiomatosis has not been studied so far.Seven placentae with chorioangiomas (n=6) or chorangiomatosis (n=1), six normal placentae, and four cutaneous haemangiomas were analysed immunohistochemically (ABC and APAAP methods) using antibodies against VEGF, NEP, KIT protein, as well as endothelial markers like PECAM-1 (CD31), CD34, v. Willebrand factor (factor VIII), and ulex europaeus. In addition, analysis of c-kit 'gain of function' mutation Asp 816 to Val by means of Hinfl digestion and direct sequencing of semi-nested polymerase chain reaction products was performed. All chorioangiomas and haemangiomas strongly expressed the endothelial markers CD34, CD31, and FVIII, while only weak expression of ulex lectin was noted. Disseminated groups of VEGF-, NEP-, and KIT protein-positive spindle cells, which coexpressed vimentin and smooth-muscle actin were identified as myofibroblasts in the stroma of four chorioangiomas. These spindle cells were quantified as numerous in two and as rare in two other cases. No VEGF-positive myofibroblasts, however, were detected in the villous stroma of normal control placentae and haemangiomas. Only scattered perivascular myofibroblasts expressing KIT protein and NEP were detected in early gestational placenta controls. In all chorioangiomas and chorangiomatosis PCR analysis failed to unveil c-kit 'gain of function' mutation Asp 816 to Val in KIT protein-positive spindle cells. Moreover, a significant increase in mast cells was observed only in the haemangiomas. As expected, endothelial origin of chorioangiomas/chorangiomatosis was verified by CD31, CD34, FVIII expression. Myofibroblastic spindle cells expressing VEGF and NEP may be precursor cells in these peculiar angiomatous tumours. Although activating c-kit mutation Asp 816 to Val was not detected by PCR, the presence of KIT protein (CD117)-positive intratumoral myofibroblastic spindle cells in chorioangiomas and chorangiomatosis might suggest involvement of the stem cell factor (SCF)-receptor in pathologically enhanced angiogenesis.
Placenta 2003 Aug
PMID:VEGF-, KIT protein- and neutral endopeptidase (NEP/CD10)-positive myofibroblasts-precursors of angiogenesis in chorioangiomas? 1285 66