ArticleCell death & disease2017
Augmented trophoblast cell death in preeclampsia can proceed via ceramide-mediated necroptosis.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 68 citations in OpenAlex.
- USP22 suppresses trophoblast cell necroptosis in preeclampsia by stabilizing KAT2A-mediated histone acetylation at the SFRP1 promoter.Journal of translational medicine · 2026Article
- Single-cell and spatial transcriptomics identify SPP1 + trophoblast necroptosis as a potential contributor to late-onset preeclampsia via SPP1-CD44-mediated interaction with macrophages.Journal of translational medicine · 2026Article
- Caspase-3/GSDME-Mediated Trophoblast Pyroptosis and Reciprocal Macrophage Polarization Contribute to Inflammation in Early-Onset Preeclampsia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Trophoblast Fusion in Hypertensive Disorders of Pregnancy and Preeclampsia.International journal of molecular sciences · 2025Review
- Tracing the Lipid Fingerprints of Preeclampsia.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- The regulated cell death at the maternal-fetal interface: beneficial or detrimental?Cell death discovery · 2024Review
- Lipid profile of circulating placental extracellular vesicles during pregnancy identifies foetal growth restriction risk.Journal of extracellular vesicles · 2024Article
- Exogenous Hydrogen Sulfide Prevents Necroptosis by Inhibiting p38MAPK Pathway Activation in JEG-3 Trophoblast Cells: A Role in Preeclampsia.Gynecologic and obstetric investigation · 2024Article
- Ceramides during Pregnancy and Obstetrical Adverse Outcomes.Metabolites · 2023Review
- MLKL regulates Cx43 ubiquitinational degradation and mediates neuronal necroptosis in ipsilateral thalamus after focal cortical infarction.Molecular brain · 2023Article
- Role of necroptosis and immune infiltration in preeclampsia: novel insights from bioinformatics analyses.BMC pregnancy and childbirth · 2023Article
- Distinct Changes in Placental Ceramide Metabolism Characterize Type 1 and 2 Diabetic Pregnancies with Fetal Macrosomia or Preeclampsia.Biomedicines · 2023Article
- Article
- RIPK1 and RIPK3 are positive prognosticators for cervical cancer patients and C2 ceramide can inhibit tumor cell proliferationFrontiers in oncology · 2023Article
- Role of Ceramides and Lysosomes in Extracellular Vesicle Biogenesis, Cargo Sorting and Release.International journal of molecular sciences · 2022Review
- Dissecting the Roles of Lipids in Preeclampsia.Metabolites · 2022Review
- Ferroptosis-Related Proteins Are Potential Diagnostic Molecular Markers for Patients with Preeclampsia.Biology · 2022Article
- The Targeting of Nuclear Factor Kappa B by Drugs Adopted for the Prevention and Treatment of Preeclampsia.International journal of molecular sciences · 2022Review
- Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation.BMJ open · 2021Article
- miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia.Biological research · 2021Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Preeclampsia, a serious hypertensive disorder of pregnancy, is characterized by elevated ceramide (CER) content that is responsible for heightened trophoblast cell death rates via apoptosis and autophagy. Whether trophoblast cells undergo necroptosis, a newly characterized form of regulated necrosis, and the potential role of CER in this process remain to be established. Herein, we report that exposure of both JEG3 cells and primary isolated cytotrophoblasts to C16:0 CER in conjunction with a caspase-8 inhibitor (Q-VD-OPh) promoted necroptotic cell death, as evidenced by increased expression and association of receptor-interacting protein kinases RIP1 and RIP3, as well as phosphorylation of mixed lineage kinase domain-like (MLKL) protein. MLKL activation and oligomerization could be abrogated by pretreatment with the necroptosis inhibitor necrostatin-1 (Nec-1). CER+Q-VD-OPH-treated primary trophoblasts displayed striking necrotic morphology along with disrupted fusion processes as evidenced by maintenance of E-cadherin-stained membrane boundaries and reduced glial cell missing-1 expression, but these events were effectively reversed using Nec-1. Of clinical relevance, we established an increased susceptibility to necroptotic cell death in preeclamptic placentae relative to normotensive controls. In preeclampsia, increased necrosome (RIP1/RIP3) protein levels, as well as MLKL activation and oligomerization associated with necrotic cytotrophoblast morphology. In addition, caspase-8 activity was reduced in severe early-onset preeclampsia cases. This study is the first to report that trophoblast cells undergo CER-induced necroptotic cell death, thereby contributing to the increased placental dysfunction and cell death found in preeclampsia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.