ArticleAutophagy2015
Disruption of sphingolipid metabolism augments ceramide-induced autophagy in preeclampsia.
Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 152 citations in OpenAlex.
- Reduced serum acetyl-L-carnitine is associated with hypertensive disorders in women with gestational diabetes mellitus: a multi-omics study.Cardiovascular diabetology · 2026Article
- Prenatal Dibutyl Phthalate Exposure Dysregulates Fetal-Placental Vascular Function and Placental Vasculature-Specific Lipid Metabolism.bioRxiv : the preprint server for biology · 2026Article
- Revised Two-Stage Model of Preeclampsia Based on Autophagic Dysfunction: A Comprehensive Review.Biomolecules · 2026Review
- Metabolic, microbial, and pharmacological stimuli elicit distinct lipidomic and cytokine responses in the human placenta.Molecular human reproduction · 2026Article
- Lipidomic signatures in maternal blood and placenta: Systematic evidence linking lipid profiles to pregnancy outcomes and fetal growth.Metabolism open · 2025Review
- Acid sphingomyelinase is a gatekeeper of placental labyrinthine architecture and function.Development (Cambridge, England) · 2025Article
- Sphingosine-1-Phosphate, a Marker of Endothelial Injury and Disease Severity in Preeclampsia.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Trophoblast Fusion in Hypertensive Disorders of Pregnancy and Preeclampsia.International journal of molecular sciences · 2025Review
- Genetic regulation and variation of fetal plasma metabolome in the context of sex, paternal breeds and variable fetal weight.Open biology · 2025Article
- Unraveling sphingolipid dynamics in late-onset preeclampsia: insights from lipidomic analysis.Biochemia medica · 2025Article
- Spatial metabolomics and transcriptomics reveal cell type-specific dynamics in the placenta of patients with late-onset preeclampsia.Frontiers in cell and developmental biology · 2025Article
- Tracing the Lipid Fingerprints of Preeclampsia.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- Metabolic disorder of nutrients-an emerging field in the pathogenesis of preeclampsia.Frontiers in nutrition · 2025Review
- Autophagy in reproduction and pregnancy-associated diseases.iScience · 2024Review
- Early pregnancy serum PFAS are associated with alterations in the maternal lipidome.Environmental research · 2024Article
- Pregnancy Metabolic Adaptation and Changes in Placental Metabolism in Preeclampsia.Geburtshilfe und Frauenheilkunde · 2024Article
- Differences in HDL Remodeling during Healthy Pregnancy and Pregnancy with Cardiometabolic Complications.Antioxidants (Basel, Switzerland) · 2024Article
- Paradoxes: Cholesterol and Hypoxia in Preeclampsia.Biomolecules · 2024Review
- The role and intervention of mitochondrial metabolism in osteoarthritis.Molecular and cellular biochemistry · 2024Review
- Excessive ER-phagy mediated by FAM134B contributes to trophoblast cell mitochondrial dysfunction in preeclampsia.Acta biochimica et biophysica Sinica · 2024Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Bioactive sphingolipids including ceramides are involved in a variety of pathophysiological processes by regulating cell death and survival. The objective of the current study was to examine ceramide metabolism in preeclampsia, a serious disorder of pregnancy characterized by oxidative stress, and increased trophoblast cell death and autophagy. Maternal circulating and placental ceramide levels quantified by tandem mass spectrometry were elevated in pregnancies complicated by preeclampsia. Placental ceramides were elevated due to greater de novo synthesis via high serine palmitoyltransferase activity and reduced lysosomal breakdown via diminished ASAH1 expression caused by TGFB3-induced E2F4 transcriptional repression. SMPD1 activity was reduced; hence, sphingomyelin degradation by SMPD1 did not contribute to elevated ceramide levels in preeclampsia. Oxidative stress triggered similar changes in ceramide levels and acid hydrolase expression in villous explants and trophoblast cells. MALDI-imaging mass spectrometry localized the ceramide increases to the trophophoblast layers and syncytial knots of placentae from pregnancies complicated by preeclampsia. ASAH1 inhibition or ceramide treatment induced autophagy in human trophoblast cells via a shift of the BOK-MCL1 rheostat toward prodeath BOK. Pharmacological inhibition of ASAH1 activity in pregnant mice resulted in increased placental ceramide content, abnormal placentation, reduced fetal growth, and increased autophagy via a similar shift in the BOK-MCL1 system. Our results reveal that oxidative stress-induced reduction of lysosomal hydrolase activities in combination with elevated de novo synthesis leads to ceramide overload, resulting in increased trophoblast cell autophagy, and typifies preeclampsia as a sphingolipid storage disorder.
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Registered trials
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.