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

Suzuki, Takamasa; Ino, Kazuhiko; Kikkawa, Fumitaka; Uehara, C.; Kajiyama, Hiroaki; Shibata, Kiyosumi; Mizutani, Shigehiko

doi:10.1053/plac.2002.0820

Cited by 30 publications

(25 citation statements)

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“…4A). Suzuki et al reported that the PKC-and MEK/ERK-dependent pathway stimulates the differentiation of human choriocarcinoma BeWo cells, which is consistent with our results (35). We also found that FSK, an activator of the cAMP-dependent pathway, induced the hCG production by nearly 12-fold (Fig.…”

Section: The Pma-induced Pkc-and Mek/erk-dependent Pathway May Enhancsupporting

confidence: 93%

PMA-induced GCMa phosphorylation stimulates its transcriptional activity and degradation

et al. 2012

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Glial cells missing Drosophila homolog a (GCMa) is a member of the GCM transcription factor family and plays critical roles in trophoblast differentiation and placental functions. It is well established that the cyclic AMP (cAMP)-dependent pathway induces the expression and transcriptional activity of GCMa by regulating post-translational modifications of GCMa, which results in enhancement of trophoblast differentiation. We previously observed that phorbol 12-myristate 13-acetate (PMA) stimulates phosphorylation of GCMa on serines 328, 378 and 383 through the protein kinase C (PKC)-and mitogen-activated protein kinase kinase (MEK)/extracellular signalregulated kinase (ERK)-dependent pathway, which decreases the protein stability of GCMa. Here we report that PMA increases the ubiquitination level of GCMa, dependent on the phosphorylation of GCMa on serines 328, 378 and 383. We found that this phosphorylation also stimulates the transcriptional activity of GCMa. Our data indicate that the PMA-induced PKC-and MEK/ERKdependent pathway enhances the degradation as well as the transcriptional activity of GCMa. We also examined the impact of this signaling pathway on trophoblasts and the results suggest that the PKC-and MEK/ERK-dependent pathway is involved in the regulation of trophoblast differentiation.

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Section: The Pma-induced Pkc-and Mek/erk-dependent Pathway May Enhancsupporting

confidence: 93%

PMA-induced GCMa phosphorylation stimulates its transcriptional activity and degradation

et al. 2012

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“…Previous studies in BeWo cells identified PKC as an important mediator of phorbol ester-induced ERK1/2 activator (Suzuki et al, 2002). The potential involvement of PKC in forskolin-induced ERK1/2 and p38MAPK activation was investigated by using Bisindolylmaleimide I (Bis I), a specific PKC inhibitor.…”

Section: Signalling Pathways Activated By Forskolinmentioning

confidence: 99%

“…Moreover, two members of the mitogen-activated protein kinases (MAPK), ERK1/2 and p38MAPK are suggested to play important roles in trophoblast differentiation (Daoud et al, 2005;Vaillancourt et al, 2009); ERK1/2 appears to be involved in phorbol ester induced trophoblast differentiation though PKC-dependent pathways (Suzuki et al, 2002). The activity of this pathway appears to be negatively regulated by Src kinases (Daoud et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Interplay of cAMP and MAPK pathways in hCG secretion and fusogenic gene expression in a trophoblast cell line

Delidaki

Hein

et al. 2011

Molecular and Cellular Endocrinology

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. Interplay of cAMP and MAPK pathways in hCG secretion and fusogenic gene expression in a trophoblast cell line. Molecular and Cellular Endocrinology, Elsevier, 2010, 332 (1-2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 of 32A c c e p t e d M a n u s c r i p t respectively) the transcription factors old astrocyte specifically-induced substance (OASIS) and glial cells missing a (GCMa) (by 3 and 6 fold, respectively) and the syncytin-2 receptor, major facilitator superfamily domain containing 2 (MFSD2) (by 2 fold). Up-regulation of AKAP79 and AKAP250, (by 2.5 and 4 fold, respectively) was also identified in forskolin-treated BeWo cells. Forskolin effects on all these genes were suppressed by chemical inhibition of p38MAPK whereas only specific genes were sensitive to ERK1/2 inhibition. This data provide novel insights into the signalling molecules and mechanisms regulating fusogenic gene expression by the adenylyl cyclase pathway.

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“…Neutral endopeptidase is found in many tissues, including vascular tissue, and its activity is increased by fatty acids and glucose in human microvascular cells (13)(14)(15)(16)(17). Interestingly, neutral endopeptidase activity has been shown to be activated by protein kinase C, which is increased in vascular tissues by diabetes (18,19). Neutral endopeptidase degrades natriuretic peptides, adrenomedullin, bradykinin, and endothelin (20).…”

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Treatment of Streptozotocin-Induced Diabetic Rats With AVE7688, a Vasopeptidase Inhibitor

et al. 2007

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In epineurial arterioles, acetylcholine-mediated vascular relaxation is mediated by nitric oxide and endotheliumderived hyperpolarizing factor (EDHF), and both mechanisms are impaired by diabetes. The mediator responsible for the effect of EDHF is unknown. In epineurial arterioles, C-type natriuretic peptide (CNP) has properties consistent with EDHF-like activity. Epineurial arterioles express CNP, and exogenous CNP causes a concentration-dependent vascular relaxation. In streptozotocin-induced diabetic rats, CNP-mediated vascular relaxation in epineurial arterioles is decreased. Since CNP may be a regulator of vascular function, a vasopeptidase inhibitor may be an effective treatment for diabetes-induced vascular and neural disease. Vasopeptidase inhibitors inhibit ACE activity and neutral endopeptidase, which degrades natriuretic peptides. Streptozotocin-induced diabetic rats were treated with AVE7688 (450 mg/kg in the diet), a vasopeptidase inhibitor, for 8 -10 weeks after 4 weeks of untreated diabetes. Treatment of diabetic rats corrected the diabetesinduced decrease in endoneurial blood flow, significantly improved motor and sensory nerve conduction velocity, prevented the development of hypoalgesia in the hind paw, and reduced superoxide and nitrotyrosine levels in epineurial arterioles. The diabetes-induced decrease in acetylcholine-mediated vascular relaxation by epineurial arterioles was significantly improved with treatment. These studies suggest that vasopeptidase inhibitors may be an effective approach for the treatment of diabetic vascular and neural dysfunction. Diabetes 56:355-362, 2007 S tudies performed in our laboratory with streptozotocin-induced diabetic rats have provided evidence that the generation of oxidative stress through the production of superoxide and peroxynitrite impairs vascular function of epineurial arterioles of the sciatic nerve, and this precedes slowing of motor nerve conduction velocity (MNCV) (1-3). These studies imply that hyperglycemia-induced oxidative stress may be responsible for diabetes-induced vascular and neural dysfunction that occurs during diabetic neuropathy.We have recently reported that the ACE inhibitor Enalapril was an effective treatment for vascular and neural disease in streptozotocin-induced diabetic rats (4). These results and our studies with C-type natriuretic peptide (CNP), demonstrating its vascular relaxation properties in epineurial arterioles, provide rationale to test the effect of vasopeptidase inhibitors on diabetic neuropathy.It has been reported in mesenteric resistance arteries that release of CNP accounts for the biological activity of endothelium-derived hyperpolarizing factor (EDHF) (5,6). CNP was found to be released from endothelial cells of the perfused rat mesenteric bed in response to endotheliumdependent vasodilators such as acetylcholine (5,6). CNP induced hyperpolarization and relaxation of mesenteric artery vascular smooth muscle through activation of natriuretic peptide receptor subtype B and the same potassium channels that...

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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

Cited by 30 publications

References 38 publications

PMA-induced GCMa phosphorylation stimulates its transcriptional activity and degradation

PMA-induced GCMa phosphorylation stimulates its transcriptional activity and degradation

Interplay of cAMP and MAPK pathways in hCG secretion and fusogenic gene expression in a trophoblast cell line

Treatment of Streptozotocin-Induced Diabetic Rats With AVE7688, a Vasopeptidase Inhibitor

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