Abstract:
:Placentas from women with preeclampsia overexpress the hypoxia-inducible transcription factor proteins, HIF-1alpha and -2alpha (Rajakumar 2001, Biol Reprod 64; p499-506 and p1019-1020). As a first step in evaluating whether HIF-alpha overexpressed in preeclamptic placentae is capable of transactivation, we tested its ability to bind to the DNA hypoxia response element (HRE). Six pairs of normal and preeclamptic placentae obtained by cesarean section were investigated. Three biopsy sites per placenta were analyzed. We first confirmed HIF-1alpha protein overexpression in the preeclamptic placentae using Western analysis. The ratios of the arbitrary densitometry units for HIF-1alpha protein from the preeclamptic and normal placentae (PE/NP) in the three biopsy sites were: 1.9 +/- 0.3, 1.7 +/- 0.2 and 1.8 +/- 0.2, each p < 0.05 vs 1.0. (A ratio of >1.0 indicates that HIF-1alpha protein expression in placentas of women with PE exceeds that in placentas of NP women.) Conventional methods for extracting nuclear proteins and subsequent analysis by electrophoretic mobility shift assay were not suited for the frozen, archived samples (data not shown). Therefore, we employed DNA affinity chromatography using a biotinylated oligonucleotide representing the HRE of the erythropoietin gene coupled to streptavidin-coated Dynabeads. The HRE-bound proteins were then characterized by Western blot analysis. The PE/NP ratios of HRE-bound HIF-1alpha in the three biopsy sites from the six pairs of normal and preeclamptic placentae were 1.7 +/- 0.2, 2.1 +/- 0.4 and 2.4 +/- 0.5, each p < 0.05 vs 1.0. Having established DNA-binding potential at least in vitro, we subsequently analyzed three proteins that have been shown to be regulated by HIF-alpha as downstream, molecular markers of HIF-1alpha activity in vivo. VEGF receptor Flt-1 and Flk-1 play key roles in angiogenesis. Tyrosine hydroxylase is the rate-limiting enzyme in catecholamine synthesis. All three genes contain functional HRE in their promoter sequences. Total proteins were extracted from the same biopsy samples that were used for total and HRE-bound HIF-1alpha. Using specific antibodies we performed Western analysis and the levels of these three proteins were quantitated. The Flt-1 and tyrosine hydroxylase proteins were significantly higher, and Flk-1 significantly lower in placentae from preeclamptic compared to normal pregnancies. In summary, HIF-1alpha protein overexpressed in preeclamptic placentae is capable of binding to its DNA recognition sequence in vitro, and modulates gene expression in vivo.
journal_name
Placentajournal_title
Placentaauthors
Rajakumar A,Brandon HM,Daftary A,Ness R,Conrad KPdoi
10.1016/j.placenta.2004.02.011keywords:
subject
Has Abstractpub_date
2004-11-01 00:00:00pages
763-9issue
10eissn
0143-4004issn
1532-3102pii
S0143400404000797journal_volume
25pub_type
杂志文章相关文献
PLACENTA文献大全abstract::Preeclampsia (PE) is a serious pregnancy-related syndrome, which is characterized by gestational hypertension and proteinuria. The microRNA-93 (miR-93) is upregulated in the maternal plasma of patients with PE. However, the functional role of miR-93 in PE remains unknown. Here, we identified that miR-93 inhibits troph...
journal_title:Placenta
pub_type: 杂志文章,收录出版
doi:10.1016/j.placenta.2017.03.008
更新日期:2017-05-01 00:00:00
abstract::Interleukin (IL)-17 is a proinflammatory cytokine with pleiotropic activities including inducing neovascularization and production of proangiogenic molecules. As pregnancy outcome depends on the balance of Th1-like/Th2-like cytokines and an increased blood supply to the fetoplacental unit, the expression of IL-17 mRNA...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2006.01.016
更新日期:2007-01-01 00:00:00
abstract::The deportation of trophoblast debris from the placenta was first documented over 100 years ago, and today we know that the deported material ranges from multinucleated syncytial knots/sprouts to trophoblast-derived nanoparticles. However little is known about the effect of trophoblast debris on maternal physiology si...
journal_title:Placenta
pub_type: 杂志文章,评审
doi:10.1016/j.placenta.2011.06.019
更新日期:2011-10-01 00:00:00
abstract::Human amniotic epithelium from patients with normal pregnancy (normal amniotic epithelium) and from patients with materno-fetal rhesus incompatibility has been examined under the light and electron microscope. In comparison with normal amniotic epithelium, the epithelium in rhesus incompatibility displays the followin...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/s0143-4004(81)80038-0
更新日期:1981-01-01 00:00:00
abstract::Paracellular pathways in the haemotrichorial placenta of the rat were studied by electron microscopy using lanthanum hydroxide as an electron dense marker. Near term placentae were dually perfused in situ, adding lanthanum to the fetal perfusate. In some placentae outflow pressure on the fetal side was elevated (betwe...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1053/plac.2000.0558
更新日期:2000-09-01 00:00:00
abstract::Intrauterine inflammation contributes to neonatal infection-related morbidity. A new histological framework of placental inflammation has recently been proposed; however, the association between this method and clinical findings has not been defined. To assess the clinical relevance of this system, we studied placenta...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2015.10.021
更新日期:2015-12-01 00:00:00
abstract::Maternal feed allowance during pregnancy can affect the development of the ovine placenta and fetus. The impact of variations in feed allowance prior to as well as throughout pregnancy has received less attention. Ewes were offered 0.6 (R), 1.2 (C) or 1.8 (AL) maintenance requirements from 89 days before conception un...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2008.02.014
更新日期:2008-06-01 00:00:00
abstract::Several xenobiotic-metabolizing mono-oxygenase activities, in conjunction with the immunohistochemical localization of the respective cytochrome P-450 forms, were investigated in placentae from smoking and non-smoking women. The antibodies used in the immunohistochemical analyses were monoclonal antibodies (MAbs) 1-7-...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/0143-4004(88)90034-3
更新日期:1988-05-01 00:00:00
abstract::Bovine nuclear transfer pregnancies are characterized by a high incidence of placental abnormalities, notably, increased placentome size and deficiencies in trophoblast cell function and establishment of placental vasculature. Alterations in gene expression during placental growth and development may contribute to the...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2005.03.002
更新日期:2006-02-01 00:00:00
abstract:INTRODUCTION:The purpose of this study was to define gross patterns of umbilical cord hypercoiling and determine correlations with histological features in the placenta and/or perinatal outcomes such as stillbirth. METHODS:Gross images of placentas with hypercoiled umbilical cords (>3 coils/10 cm) were assigned a majo...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2013.04.002
更新日期:2013-07-01 00:00:00
abstract::The placental renin-angiotensin system (RAS) is involved in placentation. We have shown that prorenin mRNA (REN) is expressed in a first trimester trophoblast cell line (HTR-8/SVneo) but not in a choriocarcinoma cell line (BeWo). We attempted to stimulate RAS expression in these cells by cAMP, 5'-aza-2'-deoxycytidine ...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2012.12.018
更新日期:2013-03-01 00:00:00
abstract:INTRODUCTION:Decidual leukocytes are critical to the development of the fetomaternal interface, regulating tolerance to the semi-allogeneic fetus and vascular transformation of the uterine spiral arteries. Despite the continuation of these processes beyond the first trimester of pregnancy, the second trimester has larg...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2014.09.018
更新日期:2014-12-01 00:00:00
abstract::It will be apparent from this review that the exact role of IFN on human placental development remains largely undefined. However, there is now sufficient data available on the biological functions of this cytokine in other cellular systems to provide a conceptual framework upon which the influence of IFN on the human...
journal_title:Placenta
pub_type: 杂志文章,评审
doi:10.1016/s0143-4004(05)80220-6
更新日期:1990-07-01 00:00:00
abstract:INTRODUCTION:The objective of this study was to explore serum levels of differentially abundant proteins between women with hypertensive disorders of pregnancy (HDP) and women with normal-term pregnancy, and to explore the contribution of SH3BGRL3 to the pathogenesis of HDP. METHODS:At 6-20 weeks gestation 48 pregnant...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2020.10.031
更新日期:2020-11-14 00:00:00
abstract:OBJECTIVE:Increasing evidence suggests an association between periodontal disease and low birthweight (LBW); however the underlying molecular mechanisms are yet to be fully elucidated. In this study, we performed a microarray analysis to observe the human placental trophoblast-like BeWo cells response to lipopolysaccha...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2010.10.007
更新日期:2011-01-01 00:00:00
abstract::Placental protein 5 (PP5)/tissue factor pathway inhibitor-2 (TFPI-2), a serine proteinase inhibitor, is homologous to tissue factor pathway inhibitor (TFPI) and commonly found in peripheral blood of pregnant woman. Although TFPI is well known to be synthesized primarily in endothelium and to play an important role in ...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1053/plac.2001.0774
更新日期:2002-02-01 00:00:00
abstract::Decidualization process involves the morphological and functional transformation of endometrial stromal cells into decidual cells. This is a finely regulated process, which involves proliferation and differentiation of stromal cells into decidual cells, which is followed by regression of the decidual tissue, mainly by...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2011.03.007
更新日期:2011-06-01 00:00:00
abstract::Parathyroid hormone-related protein (PTHrP), the major factor responsible for hypercalcaemia of malignancy, is widely expressed in normal adult and fetal tissues. In this study, the distribution of PTHrP was examined in human term placenta and membranes by immunohistochemistry using antisera to PTHrP 1-34 and 37-67. P...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/s0143-4004(05)80411-4
更新日期:1994-09-01 00:00:00
abstract::The ovaries and uteri were removed from four pregnant camels on days 14, 25, 35 and 56 after ovulation. The day 14 and 25 uteri were perfuse-fixed with 3 per cent glutaraldehyde: 3 per cent paraformaldehyde whereas the day 35 and 56 specimens were opened dorsally for photography before biopsies of allantochorion attac...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/s0143-4004(96)90046-6
更新日期:1996-05-01 00:00:00
abstract::Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At IFPA meeting 2013 there were twelve themed workshops, three of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of placent...
journal_title:Placenta
pub_type:
doi:10.1016/j.placenta.2013.11.009
更新日期:2014-02-01 00:00:00
abstract:INTRODUCTION:The ratio of birthweight to placental weight (BW:PW) is often used as a measure of placental efficiency in humans and animals. However, ratios have properties that are known to lead to spurious results. An alternative approach is the use of residuals from regression, which reflect whether birthweight is hi...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2018.06.311
更新日期:2018-08-01 00:00:00
abstract:INTRODUCTION:Visualization of the retroplacental clear space (RPCS) may provide critical insight into the development of abnormally invasive placenta (AIP). In this pre-clinical study, we characterized the appearance of the RPCS on magnetic resonance imaging (MRI) during the second half of gestation using a liposomal g...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2019.01.017
更新日期:2019-02-01 00:00:00
abstract:INTRODUCTION:Preeclampsia is characterized by maternal endothelial dysfunction. While the mechanisms leading to preeclampsia are unclear, a factor(s) from the placenta is responsible for triggering the disease. One placental factor implicated in triggering preeclampsia is trophoblast debris which may transmit pathogeni...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2014.07.009
更新日期:2014-10-01 00:00:00
abstract::Neuropeptides play an important role in the regional regulation of blood flow and hormone secretion. Few studies report the presence of peptides in the human placenta. Our experiment evaluates neuropeptides in the human placenta using immunocytochemical techniques. Representative tissue sections from full-term placent...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/s0143-4004(96)90023-5
更新日期:1996-09-01 00:00:00
abstract::A long and productive history of studies at high altitude has demonstrated that chronic hypoxia plays a key role in the aetiology of intrauterine growth restriction (IUGR) and pre-eclampsia. Susceptibility to altitude-associated IUGR varies among high-altitude populations in relation to their duration of altitude expo...
journal_title:Placenta
pub_type: 杂志文章,多中心研究,评审
doi:10.1016/j.placenta.2004.01.008
更新日期:2004-04-01 00:00:00
abstract::We present a case of intra-amniotic umbilical vein varix with thrombosis using conventional two-dimensional (2D) sonography, power Doppler, three-dimensional (3D) HD-flow, and HDlive at 35 weeks of gestation. 2D sonography showed a large banana-like umbilical cord enlargement (100 × 43.3 × 45.9 mm) including umbilical...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2013.08.008
更新日期:2013-11-01 00:00:00
abstract::Although secretory phospholipase A2 (PLA2) isozymes have been identified in human gestational tissues, their role in homeostasis and pathophysiology during pregnancy has yet to be clearly established. The aims of this brief commentary are: (1) to review recent data concerning the expression of secretory PLA2 isozymes ...
journal_title:Placenta
pub_type: 杂志文章,评审
doi:10.1016/s0143-4004(98)90093-5
更新日期:1998-01-01 00:00:00
abstract::Abnormalities in glucose metabolism linked to D-chiro-inostol phosphoglycans (IPGs) have been described in human placentas of preeclamptic women. In this study, a semi-quantitative approach to assess the histological assessment of IPGs revealed no significant differences between early and late onset preeclampsia and g...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2012.07.007
更新日期:2012-10-01 00:00:00
abstract::The present study was designed to quantify the major cellular metabolites in human placentae and their changes due to the confounding effect of time and subsequent hypoxia during sample collection using magnetic resonance spectroscopy ((1)H-and (31)P-MRS). The absolute placental concentrations of lactate, glucose, maj...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1053/plac.2002.0908
更新日期:2003-02-01 00:00:00
abstract:INTRODUCTION:Preeclampsia (PE) carries increased risks of cardiovascular- and metabolic diseases in mothers and offspring during the life course. While the severe early-onset PE (EOPE) phenotype originates from impaired placentation in early pregnancy, late-onset PE (LOPE) is in particular associated with pre-existing ...
journal_title:Placenta
pub_type: 杂志文章
doi:10.1016/j.placenta.2017.08.070
更新日期:2017-10-01 00:00:00