ArticleScientific reports2017
Inhibiting mevalonate pathway enzymes increases stromal cell resilience to a cholesterol-dependent cytolysin.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Prenols and prenoic acids in metabolism, disease, and aging.Journal of lipid research · 2026Review
- Single-cell mapping of cholesterol metabolism reveals FDPS as a therapeutic vulnerability in hepatocellular carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Integrated Multi-Omics Investigation of Gypenosides' Mechanisms in Lowering Hepatic Cholesterol.Biomolecules · 2025Article
- Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD.Molecular neurodegeneration · 2025Article
- Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD.Research square · 2024Article
- Altered blood gene expression in the obesity-related type 2 diabetes cluster may be causally involved in lipid metabolism: a Mendelian randomisation study.Diabetologia · 2023Article
- Statins as Potential Preventative Treatment of ETX and Multiple Pore-Forming Toxin-Induced Diseases.International journal of molecular sciences · 2023Article
- Membrane Cholesterol Content and Lipid Organization Influence Melittin and Pneumolysin Pore-Forming Activity.Toxins · 2022Article
- Cholesterol metabolism: from lipidomics to immunology.Journal of lipid research · 2022Review
- Oxysterols Protect Epithelial Cells Against Pore-Forming Toxins.Frontiers in immunology · 2022Article
- Oxysterols protect bovine endometrial cells against pore-forming toxins from pathogenic bacteria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Trueperella pyogenes pyolysin inhibits lipopolysaccharide-induced inflammatory response in endometrium stromal cells via autophagy- and ATF6-dependent mechanism.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2021Article
- Bisphosphonate inhibitors of squalene synthase protect cells against cholesterol-dependent cytolysins.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Vaginal Dysbiotic Microbiome in Women With No Symptoms of Genital Infections.Frontiers in cellular and infection microbiology · 2021Article
- Coenzyme QInternational journal of molecular sciences · 2020Review
- New Insights Into Targeting Membrane Lipids for Cancer Therapy.Frontiers in cell and developmental biology · 2020Review
- Article
- Atherosclerosis and Coenzyme QInternational journal of molecular sciences · 2019Review
- Concurrent and long-term associations between the endometrial microbiota and endometrial transcriptome in postpartum dairy cows.BMC genomics · 2019Article
- Tolerance and Innate Immunity Shape the Development of Postpartum Uterine Disease and the Impact of Endometritis in Dairy Cattle.Annual review of animal biosciences · 2019Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Animal health depends on the ability of immune cells to kill invading pathogens, and on the resilience of tissues to tolerate the presence of pathogens. Trueperella pyogenes causes tissue pathology in many mammals by secreting a cholesterol-dependent cytolysin, pyolysin (PLO), which targets stromal cells. Cellular cholesterol is derived from squalene, which is synthesized via the mevalonate pathway enzymes, including HMGCR, FDPS and FDFT1. The present study tested the hypothesis that inhibiting enzymes in the mevalonate pathway to reduce cellular cholesterol increases the resilience of stromal cells to PLO. We first verified that depleting cellular cholesterol with methyl-β-cyclodextrin increased the resilience of stromal cells to PLO. We then used siRNA to deplete mevalonate pathway enzyme gene expression, and used pharmaceutical inhibitors, atorvastatin, alendronate or zaragozic acid to inhibit the activity of HMGCR, FDPS and FDFT1, respectively. These approaches successfully reduced cellular cholesterol abundance, but mevalonate pathway enzymes did not affect cellular resilience equally. Inhibiting FDFT1 was most effective, with zaragozic acid reducing the impact of PLO on cell viability. The present study provides evidence that inhibiting FDFT1 increases stromal cell resilience to a cholesterol-dependent cytolysin.
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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.