Increased content of annexin II (p36) and p11 in human placentabrush-border membrane vesicles during syncytiotrophoblast maturation and differentiation

doi:10.1016/S0143-4004(96)80017-8

Placenta

Volume 17, Issue 8, 1996, Pages 669-676

https://doi.org/10.1016/S0143-4004(96)80017-8 Get rights and content

Abstract

Annexins are a group of proteins abundant in placental membranes where they may play diverse functional roles. Annexins are expressed in high levels in mature placenta but little is known about their presence at very early stages of gestation and later. We used the model of brush-border membrane vesicles (BBMV) at different stages of gestation to assess precise localization of some of these proteins in Syncytiotrophoblast apical membrane and to determine their appearance along the maturation process of placenta. Here we describe annexins type I, II, IV, V and VI which are present all along gestation in BBMV. Annexin II (p36) is present with the S100 like calcium-binding protein p11 in BBMV, where they can constitute heterotetrameric forms of annexin II linked to cytoskeleton structures. No variation of annexins I, IV and VI content was observed in BBMV along pregnancy. Annexin V undergoes significant decrease after 12th week, which could be related to local anticoagulant activity. Levels of annexin II and p11 increased progressively during gestation suggesting that heterotetrameric forms of annexin II play a role in the differentiation process of placenta and in function of the mature microvilli.

References (53)

AndoY. et al.
Calcium-induced intracellular cross-linking of lipocortin I by tissue transglutaminase in A431 cells
Journal of Biological Chemistry
(1991)
BennettP. et al.
The expression of phospholipase A2 and lipocortins (annexins) I, II and V in human fetal membranes and placenta in association with labour
Prostaglandins
(1994)
BoothA.G. et al.
An improved method for the preparation of human placental syncytiotrophoblast microvilli
Placenta
(1980)
BradfordM.
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
AnaIytical Biochemistry
(1976)
BraslauD.L. et al.
Synthesis of novel calcium-dependent proteins associated with mammary epithelial cell migration and differentiation
Experimental Cellular Research
(1984)
ChapH. et al.
Potential anticoagulant activity of lipocortins and other calcium/phospholipid binding proteins
Biochimie et Biophysica Acta
(1988)
CromptonM.R. et al.
Diversity in the lipocortin/calpactin Family
Cell
(1988)
CarlsonR.W. et al.
The plasma membrane of human placenta
Journal of Biological Chemistry
(1976)
DavidsonF.F. et al.
Inhibition of phospholipase A2 by ‘lipocortins’ and calpactins
Journal of Biological Chemistry
(1987)
FoxM.T. et al.
Increases in p11 and annexin II proteins correlate with differentiation in the PC12 pheochromocytoma
Biochemical and Biophysical Research Communication
(1991)

Gassama-DiagneA. et al.

Calcium-independent phospholipases from Guinea pig digestive tract as probes to study the mechanism of lipocortin

Journal of Biological Chemistry

(1990)

GruenbergJ. et al.

Annexins in membrane traffic

Trends Cell Biology

(1993)

HayashiH. et al.

Isolation and characterization of three forms of 36-kDa Ca2+-dependent actin and phospholipid-binding proteins from human placenta membrane

Biochemical and Biophysical Research Communications

(1987)

HullinF. et al.

Effect of dexamethasone on prostaglandin synthesis and on lipocortin status in human endothelial cells

Journal of Biological Chemistry

(1989)

IiokaH. et al.

Characterization of human placental activity, for transport of L-alanine, using brush border (microvillous) membrane vesicles

Placenta

(1992)

JindalH.K. et al.

The protein-tyrosine kinase substrate, Calpactin-I heavy chain (p36), is part of the primer recognition protein complex that interacts with DNApolymerase-alpha

Journal of Biological Chemistry

(1991)

KudoY. et al.

Carrier-mediated transport system for cephalex in inhuman placental brush-border membrane vesicles

Biochimica et Biophysica Acta

(1989)

KrikunG. et al.

The expression of the placental anticoagulant protein, annexin V, by villous trophoblasts: immunolocalization and in vitro regulation

Placenta

(1994)

LinH.C. et al.

Annexin VI is required for budding of clathrin-coated pits

Cell

(1992)

MossS.E. et al.

Alternative splicing gives rise to two forms of the p68 Ca2+-binding protein

Febs Letters

(1990)

RandJ.H. et al.

Reduction of annexin V (placental anticoagulant protein I) on placental villi of women with antiphospholipid antibodies and recurrent spontaneousabortion

American Journal of Obstetrics and Cynecology

(1994)

RaynalP. et al.

Annexins: the problem of assessing the biological role for a gene family of multifunctional calcium- and phospholipid-binding proteins

Biochimica et Biophysica Acta

(1994)

RaynalP. et al.

Morphological and biochemical evidence for partial nuclear localization of annexin 1 in endothelial cells

Biochemical and Biophysical Research Communication

(1992)

SallesJ.P. et al.

Sustained effect of angiotensin II on tyrosine phosphorylation of annexin I in glomerular mesangial cells

Journal of Biological Chemistry

(1993)

SmithC.H. et al.

Characterization of a microvillous membrane preparation from human placental syncytiotrophoblast: a morphologic, biochemical, and physiologic study

American Journal of Obstetrics and Gynecology

(1977)

BarneaE.R. et al.

The First Twelve Weeks of Gestation

(1992)

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Thus, the results demonstrate that S100A9 is associated with preeclampsia through activation of the NLRP3 inflammasome [143]. It has been also found that another member of the S100 family, S100A10, together with annexin 2 (A2) is expressed on the brush border of placental syncytiotrophoblasts and seems to play a role in the differentiation process of placenta and in functioning of mature microvilli [144]. As to preeclampsia, the serum level of S100A10 is elevated when compared to healthy pregnancy [145].
S100 proteins bind Ca²⁺ and regulate various signaling pathways inside and outside the cell. They are expressed in vertebrates and exhibit tissue and cell specific distribution. Of note, increased level of S100 proteins is observed in different pathologies such as cancers, nervous system diseases/neurodegeneration, inflammation or cardiovascular diseases. Certain S100 proteins can be found in serum and/or other body fluids, at an especially high level in pathological states. Thus, S100 proteins might serve as diagnostic markers in the clinic. Interestingly, expression of many S100 proteins is found to be associated with pregnancy, which suggests that alterations in their expression during pregnancy may regulate processes involved in embryo/fetus formation. In this review we summarize available literature data concerning the expression and possible function of S100 proteins in a disease of pregnant women known as preeclampsia or EPH-gestosis.
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Deficient anticoagulant activity of annexin A5 and deficient profibrinolytic activity of annexin A2 have been linked to increased risk of thrombotic events. Placental dysfunction due to fibrin deposition/microthrombi has been implicated in the pathogenesis of pre-eclampsia (PE). In this study, we aimed to assess serum levels of annexin A5 and annexin A2 in a cohort of PE patients and investigate their role as biomarkers for the development of the disease. We examined 80 women in total; 40 healthy pregnant women and 40 pregnant women with PE after 20 weeks of pregnancy. Women were subjected to full clinical assessment, ultrasonography, and laboratory testing including complete blood picture, liver and kidney function tests and assessment of serum and urine proteins. Annexin A5 and annexin A2 were analyzed using enzyme-linked immunosorbent assay. The study showed serum annexin A2 but not annexin A5 was significantly reduced (P = 0.029) in women with PE (total and severe cases) compared to those with normal pregnancy. The ROC analysis of annexin A2 level for the prediction of development of PE showed an area under the curve of 0.64 (P = 0.029), and the best cut-off value was 0.89 ng/ml with a sensitivity of 70.0% and a specificity of 70.0%. Univariate analysis showed annexin A2 of <0.89 ng/ml, proteinuria, lower platelet count and higher BP were associated with significantly higher risk to develop PE. Based on this pilot study, serum annexin A2 levels may be a useful biomarker for pre-eclampsia. However, a larger study is required before a final conclusion is made.
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Citation Excerpt :
Annexins are involved in various cellular processes such as exocytosis, endocytosis, regulation of ion channel activity, and stabilization of membrane domains (Gerke and Moss, 2002). Annexins are abundant in placental membranes (Kaczan-Bourgois et al., 1996). Within the annexin family, annexin A2 (ANXA2) and annexin A5 (ANXA5) possess profibrinolytic (Ling et al., 2004; Ishii et al., 2001) and antithrombotic activities (Ueki et al., 2012), respectively.
Acquired and inherited thrombophilia have both been reported to be associated with an increased risk of obstetric complications in early or later stages of pregnancy. Annexin A2 (ANXA2) is strongly expressed in vascular and placental tissues and plays a crucial role in fibrinolysis. The aim of the present study was to evaluate the prevalence of antibodies directed against ANXA2 in patients with recurrent miscarriage or obstetric complications. Anti-ANXA2 antibodies (aANXA2) were detected by ELISA in the sera from 46 women with obstetric morbidity, mainly recurrent miscarriage. The cut-off value for positivity was defined as 3 standard deviations above the mean optical density (OD) obtained in the sera from 42 female blood donors. The prevalence of aANXA2 in patients and healthy individuals was 15.2% and 2.3%, respectively. A statistically significant difference was observed between the 2 groups in terms of aANXA2 IgG titers (p = 0.01). The highest aANXA2 levels were observed in sera from 2 patients with recurrent miscarriage and one patient with preeclampsia. aANXA2 could play a role in thrombotic mechanisms leading to recurrent pregnancy loss and placental vascular disease. Further studies are needed to determine whether ANXA2 is critical for maintenance of placental integrity.
Annexin A2 autoantibodies in thrombosis and autoimmune diseases
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The present review will focus on annexin A2 (ANXA2, also known as annexin II, lipocortin II and p36) and anti-ANXA2 autoAb. Anti-ANXA2 autoantibodies target ANXA2 which is a 36 kD calcium-dependent phospholipid-binding protein present in various cells such as endothelial cells, syncytiotrophoblast cells, monocytes, macrophages, mesangial cells, and a variety of tumor cells [6,7]. The N-terminal domain of ANXA2 contains a binding site for the adaptor S100A10 [4], a nuclear export sequence [8], and a reactive cysteine residue [9], while the C-terminal domain of ANXA2 contains binding sites for phospholipids, F-actin, fibrin and heparin [10].
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by arterial, venous or small-vessel thrombotic events, and recurrent miscarriages or fetal loss. APS diagnosis is based on the repeated detection of anti-phospholipid (PL) antibodies (Ab), typically associated with anti-β2 glycoprotein I (β2GPI)-Ab. Recent studies suggest that anti-β2GPI Ab activity involves a protein complex including β2GPI and annexin A2 (ANXA2). Anti-ANXA2 Ab recognizes this complex, and these Ab can effectively promote thrombosis by inhibiting plasmin generation, and by activating endothelial cells. Therefore, anti-ANXA2 Ab represent a new biomarker, which can be detected in up to 25% of APS patients. Moreover, anti-ANXA2 Ab have been detected, in thrombotic associated diseases including pre-eclampsia, in other autoimmune diseases, and in cancer.
Quantitative proteomic analysis of pregnancy-related proteins from peripheral blood mononuclear cells during pregnancy in pigs
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Information obtained from peripheral blood could help us understand the underlying mechanisms in autoimmune diseases, cancer, pregnancy, and other conditions. In this paper, we present the protein map of porcine peripheral blood mononuclear cells (PBMC) to better understand the molecular expression changes that occur during pregnancy using proteomic analysis. We detected 94 differentially expressed proteins in pregnant vs. non-pregnant (NP) pigs, and a representative set of the proteins was subjected to LC–MS/MS analysis. Furthermore, the identified proteins were categorized according to their biological process and molecular function. By classifying the proteins according to their functions, a large number of differentially regulated proteins involved in anti-oxidant, detoxification and stress response pathways were found, including peroxiredoxin (PRX) 1, 2, and 6, glutathione-S-transferase (GST), annexin A2, and A6, and heat shock protein 27 (HSP 27) during pregnancy (pregnancy d of E40, embryonic day 40; E70, embryonic day 70; and E93, embryonic day 93) compared with non-pregnancy. In this study, a proteomic approach utilizing 2-DE and LC–MS/MS was applied to evaluate specific molecular expression changes during pregnancy compared with non-pregnancy. Together, these data offer new information about the proteome map and factors that are differentially regulated during maintenance of normal pregnancy.
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Deficient fibrinolytic activity due to alterations of profibrinolytic receptor annexin A2 has been shown to be related to increased thrombosis. We compared the expression of annexin A2 in pre-eclampsia with that in normal pregnancies and investigated its relationship to placental thrombin formation.
Sixty patients with pre-eclampsia and 30 matched normal pregnant controls were included in the study. Expression of annexin A2 mRNA in placental tissues was analyzed using quantitative RT-PCR. Annexin A2 protein in placentas as well as blood was determined by western blot analysis and immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to detect the presence of anti- annexin A2 antibodies in peripheral maternal blood.
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The down regulation of annexin A2 expression and the presence of anti-annexin A2 antibodies were correlated to PE and may increase placental thrombin formation.

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Increased content of annexin II (p36) and p11 in human placentabrush-border membrane vesicles during syncytiotrophoblast maturation and differentiation

Abstract

Journal of Biological Chemistry

Prostaglandins

Placenta

AnaIytical Biochemistry

Experimental Cellular Research

Biochimie et Biophysica Acta

Cell

Journal of Biological Chemistry

Journal of Biological Chemistry

Biochemical and Biophysical Research Communication

Journal of Biological Chemistry

Trends Cell Biology

Biochemical and Biophysical Research Communications

Journal of Biological Chemistry

Placenta

Journal of Biological Chemistry

Biochimica et Biophysica Acta

Placenta

Cell

Febs Letters

American Journal of Obstetrics and Cynecology

Biochimica et Biophysica Acta

Biochemical and Biophysical Research Communication

Journal of Biological Chemistry

American Journal of Obstetrics and Gynecology

The First Twelve Weeks of Gestation