Nitric oxide protects human extravillous trophoblast cells from apoptosis by a cyclic GMP-dependent mechanism and independently of caspase 3 nitrosylation

Dash, Philip R.; Cartwright, Judith E.; Baker, Philip N.; Johnstone, Alan P.; Whitley, Guy

doi:10.1016/s0014-4827(03)00156-3

Cited by 69 publications

(62 citation statements)

References 46 publications

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“…Apoptotic cells were scored according to the time at which clear apoptotic morphology was first observed. 29 For the annexin V/PI assay, 2 ϫ 10 5 cells were seeded into a 6-well plate in RPMI 1% FCS for 24 hours and then incubated for an additional 12 hours in RPMI 0.5% FCS. Cells were left untreated or were treated with sHLA-G1 (1 g/mL), mAb CD160 (10 g/mL), or control IgG1 (10 g/mL) for 50 hours in the presence of VEGF (50 ng/mL).…”

Section: Apoptosis Assaysmentioning

confidence: 99%

Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells

Fons

Chabot

Cartwright

et al. 2006

Blood

181

149

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HLA-G is a major histocompatibility complex class Ib molecule whose constitutive tissue distribution is restricted mainly to trophoblast cells at the maternal-fetal interface during pregnancy. In this study, we demonstrated the ability of the soluble HLA-G1 (sHLA-G1) isoform to inhibit fibroblast growth factor-2 (FGF2)-induced capillary-like tubule formation. Using a rabbit corneal neovascularization model, we further showed that sHLA-G1 inhibits FGF2-induced angiogenesis in vivo. We also demonstrated that sHLA-G1 induces endothelial cell apoptosis through binding to BY55/ CD160, a glycosylphosphatidylinositolanchored receptor expressed by endothelial cells. Furthermore, we showed that the specific CL1-R2 anti-CD160 monoclonal antibody mimics sHLA-G1-mediated inhibition of endothelial cell tube formation and induction of apoptosis. Thus, the engagement of CD160 in endothelial cells may be essential for the inhibition of angiogenesis. sHLA-G1/CD160-mediated antiangiogenic property may participate in the vascular remodeling of maternal spiral arteries during pregnancy, and, given that we found that CD160 is strongly expressed in the vasculature of a murine tumor, it offers an attractive therapeutic target for preventing pathologic neovascularization. ( IntroductionHLA-G is a human major histocompatibility complex (MHC) class Ib gene characterized by a unique promoter region, limited polymorphism, restricted constitutive tissue distribution, and several spliced transcripts encoding either membrane-bound or soluble proteins. 1 The soluble HLA-G1 (sHLA-G1) isoform derives from mRNA retaining intron 4, 2 which contains a stop codon that precludes translation of the transmembrane domain. Such intron 4 retention is unique among all HLA class I molecules described to date. This 37-kDa, intron 4-retaining sHLA-G1 isoform associates noncovalently with ␤2-microglobulin (␤2m). 2 Soluble HLA-G can also be generated by metalloproteinase-mediated release of surface HLA-G containing only extracellular domains. 3 The predominant expression of sHLA-G1 in the placenta, at a time when polymorphic HLA-A and HLA-B class Ia molecules are repressed, is consistent with important immunologic functions during pregnancy. 4 sHLA-G1 induces apoptosis of activated CD8 ϩ T and natural killer (NK) cells 5,6 and down-regulates the CD4 ϩ T-cell alloproliferation response. 7 The observation that some anti-HLA-G monoclonal antibodies bound to HLA-G-negative placental endothelial cells 8,9 led to our hypothesis that sHLA-G1 might bind to these cells and be involved in the modulation of placental angiogenesis or uterine vessel remodeling. 8 Several further observations are in line with such a novel function of HLA-G. Among them is that a defect of HLA-G expression in extravillous cytotrophoblast is associated with preeclampsia, 10,11 a common complication of pregnancy in which HLA-G ϩ endovascular trophoblast invasion of maternal spiral arteries is abrogated, compromising blood flow to the maternal interface. 12 In addition, it has been shown that HL...

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Section: Apoptosis Assaysmentioning

confidence: 99%

Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells

Fons

Chabot

Cartwright

et al. 2006

Blood

181

149

View full text Add to dashboard Cite

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“…This system has been well characterized and used previously to monitor apoptosis in live culture systems. 16,21,22 The onset of apoptosis was determined as the time at which clear apoptotic morphology was first observed. Characteristic apoptotic morphology was easily identifiable in HASMCs; Figure 3A shows phase contrast images of a typical individual cell from a time-lapse sequence.…”

Section: Trophoblasts Induce Apoptosis In Arterial Smcs In Vitromentioning

confidence: 99%

Invasive Trophoblasts Stimulate Vascular Smooth Muscle Cell Apoptosis by a Fas Ligand-Dependent Mechanism

Harris

Keogh

Wareing

et al. 2006

The American Journal of Pathology

139

109

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During pregnancy, trophoblasts migrate from the placenta into uterine spiral arteries, transforming them into wide channels that lack vasoconstrictive properties. In pathological pregnancies, this process is incomplete. To define the fundamental events involved in spiral artery remodeling, we have studied the effect of trophoblasts on vascular smooth muscle cells (SMCs). Here we demonstrate for the first time that apoptosis of SMCs can be initiated by invading trophoblasts. When trophoblasts isolated from normal placenta (primary trophoblasts) or conditioned medium was perfused into spiral or umbilical artery segments, apoptosis of SMCs resulted. Culture of human aortic SMCs (HASMCs) with primary trophoblasts, primary trophoblast-conditioned medium, or a trophoblast-derived cell line (SGHPL-4) also significantly increased SMC apoptosis. Fas is expressed by spiral artery SMCs, and a Fas-activating antibody triggered HASMC apoptosis. Furthermore, a Fas ligand (FasL)-blocking antibody significantly inhibited HASMC apoptosis induced by primary trophoblasts, SGHPL-4, or trophoblast-conditioned medium. Depleting primary trophoblast-conditioned medium of FasL also abrogated SMC apoptosis in vessels in situ. These results suggest that apoptosis triggered by the release of soluble FasL from invading trophoblasts contributes to the loss of smooth muscle from the walls of spiral arteries during pregnancy.

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“…The latter effects were closely associated with lipid-rich organelles (mitochondria and endoplasmic reticulum) [28,86]. On the other hand, trophoblasts might also be protected from apoptosis via S-nitrosylation of caspase 3 [87].…”

Section: S-nitrosylation Plays Pivotal Role In Modulating Trophoblastmentioning

confidence: 98%

“…As well, no S-nitrosylations have yet been reported for polo-like kinases (PLKs), anaphase promoting factor/cyclosome (APC/C), Wee1, and Myt1, which are MPF regulators. Nevertheless, the dual specificity phosphatase Cdc25, which is the main activator of MPF, is clearly impacted by its S-nitrosylation because it annihilates its phosphatase activity [82,87]. Recently, an alternate mechanism than direct S-nitrosylation of Cdc25C for its inhibition was proposed since NOAD, a nitric oxide-releasing derivative of oleanolic acid, induced activation of Chk2, resulting in an increase of the inhibitory phosphorylation of Cdc25C on its residue Serine 216 [84].…”

Section: S-nitrosylation As a Posttranslational Modification Potentiamentioning

confidence: 99%

From Nitric Oxide Toward S-Nitrosylation: Expanding Roles in Gametes and Embryos

Ješeta¹,

Sedmı́ková²,

Bodart³

2017

Nitric Oxide Synthase - Simple Enzyme-Complex Roles

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Nitric oxide (NO) is a gasotransmitter involved in various aspects of reproduction. The observational data from different species, such as sea urchin, ascidians, amphibians, rodents, porcine, bovine, and human, suggest that NO might have a significant role in reproduction through several mechanisms. This proposed role might appear preserved through evolution; however, the effects of NO also depend on the species or stages considered. There has been debate over the physiological relevance of NO, though the benefits of its use in assisted reproduction are now widely recognized. Over the past years, S-nitrosylation has provided a new angle to decipher the mechanisms through which NO exerts its actions. This chapter summarizes, in a nonexhaustive manner, research that explores the role of NO in gametes and embryos.

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Nitric oxide protects human extravillous trophoblast cells from apoptosis by a cyclic GMP-dependent mechanism and independently of caspase 3 nitrosylation

Cited by 69 publications

References 46 publications

Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells

Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells

Invasive Trophoblasts Stimulate Vascular Smooth Muscle Cell Apoptosis by a Fas Ligand-Dependent Mechanism

From Nitric Oxide Toward S-Nitrosylation: Expanding Roles in Gametes and Embryos

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