Placental leucine aminopeptidase/oxytocinase gene regulation by activator protein‐2 in BeWo cell model of human trophoblast differentiation

Iwanaga, Kumi; Nomura, Seiji; Ito, Tomomi; Ikoma, Yoko; Yamamoto, Eiko; Okada, Mayumi; Itakura, Atsuo; Kikkawa, Fumitaka; Tsujimoto, Masafumi; Mizutani, Shigehiko

doi:10.1016/s0014-5793(03)00897-4

Cited by 15 publications

(11 citation statements)

References 27 publications

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“…The placenta-specific nature of FP2 and FP3 is intriguing given the link between AP-2␣ and AP-2␥ in the regulation of placental genes including human chorionic gonadotropin, placental leucine aminopeptidase, and CS (35)(36)(37)(38). AP-2␣ and AP-2␥ are expressed in human placenta (36) but there is evidence that AP-2␥ expression decreases whereas AP-2␣ synthesis increases with human trophoblast differentiation and syncytiotrophoblast formation (35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

“…AP-2␣ and AP-2␥ are expressed in human placenta (36) but there is evidence that AP-2␥ expression decreases whereas AP-2␣ synthesis increases with human trophoblast differentiation and syncytiotrophoblast formation (35)(36)(37). Consistent with this pattern of expression, synthesis of the human chorionic gonadotropin subunits in cytotrophoblasts is associated with AP-2␥ binding (36), whereas placental leucine aminopeptidase, which is expressed preferentially in syncytiotrophoblasts, has been linked to increased AP-2␣ binding (35). The latter, as well as the predominant expression of AP-2␣ at term (39), would be consistent with our data and the association of AP-2␣ with the HS III region in human placenta chromatin (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Binding of AP-2 and ETS-Domain Family Members Is Associated with Enhancer Activity in the Hypersensitive Site III Region of the Human Growth Hormone/Chorionic Somatomammotropin Locus

Jin

Norquay

Yang

et al. 2004

Molecular Endocrinology

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The human GH gene family is specifically expressed in somatotrophs of the anterior pituitary and placental syncytiotrophoblast. Two nuclease-hypersensitive sites, HS III and HS V, are associated with a region of chromatin located 28 and 30 kb upstream of the pituitary GH gene transcription initiation site (+1) in both pituitary and placenta nuclei. A role for this region in pituitary GH gene expression has been reported, but the potential relevance to placental gene expression has not been determined. Deletion analysis of a 5.2-kb region (nucleotides - 27,568/-32,746) containing HS III to V-related sequences localized significant enhancer activity to a 574-bp HS III fragment (nucleotides -27,676/-28,249) in multiple transfected cell lines. Four nuclease-protected regions [footprints (FP) 1-4] were identified in the 574-bp fragment. FP2 and FP3 were detected with placenta cell nuclear protein, whereas FP1 and FP4 were observed with placental and nonplacental cell nuclear extract. Disruption of FP1 had no effect on heterologous promoter activity in transfected pituitary and placental cells, whereas loss of FP2 and FP3 resulted in modest increases in placental cells, reflecting the presence of repressor activity associated with these regions in vitro. In contrast, disruption of the FP4 region by mutation or deletion significantly reduced enhancer activity. As a result, 30-fold enhancer activity was localized to a 41-bp region in transfected placental tumor cells. Binding of candidate proteins, activator protein (AP)-2 (FP3) and Elk-1 (FP4), was confirmed using competition assays with specific oligonucleotides and antibodies. Moreover, these factors were associated with the hyperacetylated HS III region in human pituitary [activator protein 2 (AP-2) and Elk-1] and term placenta (AP-2) chromatin. These data implicate AP-2 and ETS-domain family members in the regulation of the GH/CS locus and raise the possibility that different complexes form in the HS III region in placenta and pituitary cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Binding of AP-2 and ETS-Domain Family Members Is Associated with Enhancer Activity in the Hypersensitive Site III Region of the Human Growth Hormone/Chorionic Somatomammotropin Locus

Jin

Norquay

Yang

et al. 2004

Molecular Endocrinology

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“…AP-2 and ikaros were found to cooperatively enhance P-LAP transcription in trophoblastic cells. In addition, forskolin (FSK) treatment was shown to upregulate P-LAP gene expression via AP-2, putatively AP-2α, which is upregulated with trophoblast differentiation [8]. Animal studies with APA on not only APA deficient mouse but also spontaneously hypertensive rat and Dahl salt-sensitive rat suggested a pivotal role of APA via degradation of A-II in hypertension [9].…”

Section: Placental Cell Surface-aminopeptidases As a Feto-maternal Bamentioning

confidence: 99%

Embryo–Placento–Maternal Interaction and Biomarkers: From Diagnosis to Therapy – A Workshop Report

et al. 2007

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“…[31][32][33] Membrane-bound P-LAP is released into maternal blood flow via proteolytic cleavage by metalloproteases such as ADAMs, a disintegrin and metalloproteinases. [34][35][36] During normal pregnancy, P-LAP activity in maternal serum gradually increases to the maximum at near term, 30) which may be associated with the maintenance of pregnancy homeostasis and the onset of labor pains.…”

Section: Placental Leucine Aminopeptidase (P-lap)mentioning

confidence: 99%

Role of Aminopeptidases in the Blood Pressure Regulation

Mitsui

Nomura

Itakura

et al. 2004

Biological & Pharmaceutical Bulletin

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In addition to the neural and autoregulatory factors, blood pressure (BP) is regulated by humoral factors including vasoactive peptides. When evaluating the peptide actions, degradation by proteases should be also considered in addition to the generation of peptides and their receptors. This review describes the roles of aminopeptidase A, placental leucine aminopeptidase and kininase I, which are enzymes responsible for hydrolyzing angiotensin II (AngII), vasopressin (AVP) and bradykinin (BK), respectively, in BP regulation. Especially, we focus on the association of the proteases with preeclampsia, hypertensive disorder peculiar to pregnancy, since one of the representative organs that are rich in theses proteases is placenta. Although the physiological roles of the placental proteases have not been fully understood, several lines of evidence suggest that the proteases are involved in the maintenance of pregnancy homeostasis including fetal and maternal BP regulation through the metabolism of bioactive peptides at the interface between mother and fetus.

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Placental leucine aminopeptidase/oxytocinase gene regulation by activator protein‐2 in BeWo cell model of human trophoblast differentiation

Cited by 15 publications

References 27 publications

Binding of AP-2 and ETS-Domain Family Members Is Associated with Enhancer Activity in the Hypersensitive Site III Region of the Human Growth Hormone/Chorionic Somatomammotropin Locus

Binding of AP-2 and ETS-Domain Family Members Is Associated with Enhancer Activity in the Hypersensitive Site III Region of the Human Growth Hormone/Chorionic Somatomammotropin Locus

Embryo–Placento–Maternal Interaction and Biomarkers: From Diagnosis to Therapy – A Workshop Report

Role of Aminopeptidases in the Blood Pressure Regulation

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