ArticleJournal of gastroenterology2015
Indomethacin suppresses LAMP-2 expression and induces lipophagy and lipoapoptosis in rat enterocytes via the ER stress pathway.
Article in Journal of gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Selective autophagy of intracellular organelles: recent research advances.Theranostics · 2021Pooled it
- Plantamajoside mitigates endoplasmic reticulum stress-mediated pancreatic β-cell apoptosis in type 2 diabetesWorld journal of diabetes · 2025Article
- Autophagy and Its Association with Macrophages in Clonal Hematopoiesis Leading to Atherosclerosis.International journal of molecular sciences · 2025Review
- Rod-shaped mesoporous silica nanoparticles reduce bufalin cardiotoxicity and inhibit colon cancer by blocking lipophagy.Lipids in health and disease · 2024Article
- Metabolomic Studies for Metabolic Alterations Induced by Non-Steroidal Anti-Inflammatory Drugs: Mini Review.Biomolecules · 2021Review
- Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis- and autophagy-associated molecules.International journal of experimental pathology · 2020Article
- Anti-Melanoma Activity of Indomethacin Incorporated into Mesoporous Silica Nanoparticles.Pharmaceutical research · 2020Article
- Review
- NSAIDs disrupt intestinal homeostasis by suppressing macroautophagy in intestinal epithelial cells.Scientific reports · 2019Article
- Article
- Repeated administration of the NSAID meloxicam alters the plasma and urine lipidome.Scientific reports · 2019Article
- As a painkiller: a review of pre- and postnatal non-steroidal anti-inflammatory drug exposure effects on the nervous systems.Inflammopharmacology · 2018Review
- Upregulated Autophagy in Sertoli Cells of Ethanol-Treated Rats Is Associated with Induction of Inducible Nitric Oxide Synthase (iNOS), Androgen Receptor Suppression and Germ Cell Apoptosis.International journal of molecular sciences · 2017Article
- Sodium 4-phenylbutyric acid prevents murine acetaminophen hepatotoxicity by minimizing endoplasmic reticulum stress.Journal of gastroenterology · 2017Article
- Genetic ablation or pharmacologic inhibition of autophagy mitigated NSAID-associated gastric damages.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Modulation of Lipid Droplet Metabolism-A Potential Target for Therapeutic Intervention inFrontiers in microbiology · 2017Review
- Glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of ER stress/GSK-3-mediated mitochondrial pathway.Scientific reports · 2016Article
- The roles of macrophage autophagy in atherosclerosis.Acta pharmacologica Sinica · 2016Review
- Role of endoplasmic reticulum stress in drug-induced toxicity.Pharmacology research & perspectives · 2016Review
- Endoplasmic reticulum stress signaling in mammalian oocytes and embryos: life in balance.International review of cell and molecular biology · 2015Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIndomethacin enhances small intestinal epithelial cell apoptosis, which may account for mucosal ulceration. However, the involvement of autophagy in indomethacin-induced enterocyte damage is unreported.
methodsUsing light microscopy and electron microscopy techniques, Western blot analysis, and pharmacological inhibition of autophagy, we investigated the autophagic response of cultured rat enterocytes to indomethacin treatment (200 µM) at various time points. Furthermore, autophagy was examined in enterocytes of rats given indomethacin by gavage (10 mg/kg).
resultsOur data indicate that indomethacin induced accumulation of cytoplasmic lipid droplets (LDs) in cultured enterocytes, which was associated with time-dependent autophagic responses. Initially (0-6 h), mediated by endoplasmic reticulum stress and suppression of mammalian target of rapamycin, a predominant cytoprotective lipophagy was activated in indomethacin-treated enterocytes, as evidenced by induction and colocalization of LC3-II with LDs, excessive formation of autophagosomes sequestering LDs (autolipophagosomes; ALPs), and decreased viability of enterocytes on blocking autophagy with 3-methyladenine. On prolonged exposure to indomethacin (6-24 h), there was a decrease of LAMP-2 expression in enterocytes coupled with accumulation of ALPs and LDs with fewer autolysosomes in addition to an elevation of lipoapoptosis. These time-dependent autophagic and apoptotic responses to indomethacin treatment were detected in enterocytes of indomethacin-treated rats, confirming in vitro results.
conclusionsThe findings of this study describe a novel mechanism of enterocyte damage by indomethacin mediated by endoplasmic reticulum stress, accumulation of LDs, and subsequent activation of the early phase of cytoprotective lipophagy. This is followed by a late phase characterized by reduced expression of lysosomal autophagic proteins, accumulation of ALPs, and enhanced lipoapoptosis.
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