ArticleCell death & disease2012
Apoptosis, autophagy and ER stress in mevalonate cascade inhibition-induced cell death of human atrial fibroblasts.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 123 citations in OpenAlex.
- Simvastatin-Induced Ferroptosis in Orbital Fibroblasts in Graves' Ophthalmopathy.Investigative ophthalmology & visual science · 2025Article
- Mechanisms of the Mitochondrial Unfolded Protein Response in Caenorhabditis elegans and Mammals and Its Roles in Striated Muscles.Aging and disease · 2024Review
- Targeted Mevalonate Pathway and Autophagy in Antitumor Immunotherapy.Current cancer drug targets · 2024Review
- Genetic insights into repurposing statins for hyperthyroidism prevention: a drug-target Mendelian randomization study.Frontiers in endocrinology · 2024Article
- The Essential Strategies to Mitigate Cardiotoxicity Caused by Doxorubicin.Life (Basel, Switzerland) · 2023Review
- Article
- Lipid rafts disruption by statins negatively impacts the interaction between SARS-CoV-2 S1 subunit and ACE2 in intestinal epithelial cells.Frontiers in microbiology · 2023Article
- Cardiotoxicity as a Possible Side Effect of Statins.Reviews in cardiovascular medicine · 2023Review
- Regulation of cardiac fibroblast cell death by unfolded protein response signaling.Frontiers in physiology · 2023Review
- Pharmacological Activities of Ginkgolic Acids in Relation to Autophagy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Review of Recent Laboratory and Experimental Data on Cardiotoxicity of Statins.Journal of cardiovascular development and disease · 2022Review
- Novel Effects of Statins on Cancer via Autophagy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Endoplasmic Reticulum Stress in Colonic Mucosa of Ulcerative Colitis Patients Is Mediated by PERK and IRE1 Pathway Activation.Mediators of inflammation · 2022Article
- Article
- Effect of pulsatile stretch on unfolded protein response in a new model of the pulmonary hypertensive vascular wall.Biochemistry and biophysics reports · 2021Article
- Autophagy, Apoptosis, the Unfolded Protein Response, and Lung Function in Idiopathic Pulmonary Fibrosis.Cells · 2021Article
- Regulation of endoplasmic reticulum stress and trophectoderm lineage specification by the mevalonate pathway in the mouse preimplantation embryo.Molecular human reproduction · 2021Article
- Mevalonate Pathway-mediated ER Homeostasis Is Required for Haploid Stability in Human Somatic Cells.Cell structure and function · 2021Article
- Mechanisms Targeting the Unfolded Protein Response in Asthma.American journal of respiratory cell and molecular biology · 2021Review
- Simvastatin Inhibits CYR61 Expression in Orbital Fibroblasts in Graves' Ophthalmopathy through the Regulation of FoxO3a Signaling.Mediators of inflammation · 2021Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) are cholesterol-lowering drugs that exert other cellular effects and underlie their beneficial health effects, including those associated with myocardial remodeling. We recently demonstrated that statins induces apoptosis and autophagy in human lung mesenchymal cells. Here, we extend our knowledge showing that statins simultaneously induces activation of the apoptosis, autophagy and the unfolded protein response (UPR) in primary human atrial fibroblasts (hATF). Thus we tested the degree to which coordination exists between signaling from mitochondria, endoplasmic reticulum and lysosomes during response to simvastatin exposure. Pharmacologic blockade of the activation of ER-dependent cysteine-dependent aspartate-directed protease (caspase)-4 and lysosomal cathepsin-B and -L significantly decreased simvastatin-induced cell death. Simvastatin altered total abundance and the mitochondrial fraction of proapoptotic and antiapoptotic proteins, while c-Jun N-terminal kinase/stress-activated protein kinase mediated effects on B-cell lymphoma 2 expression. Chemical inhibition of autophagy flux with bafilomycin-A1 augmented simvastatin-induced caspase activation, UPR and cell death. In mouse embryonic fibroblasts that are deficient in autophagy protein 5 and refractory to autophagy induction, caspase-7 and UPR were hyper-induced upon treatment with simvastatin. These data demonstrate that mevalonate cascade inhibition-induced death of hATF manifests from a complex mechanism involving co-regulation of apoptosis, autophagy and UPR. Furthermore, autophagy has a crucial role in determining the extent of ER stress, UPR and permissiveness of hATF to cell death induced by statins.
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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.