ArticleMolecular and cellular biology2004
NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers.
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Who cites it
198 citing papers in PubMed, 423 citations in OpenAlex.
- 7-ketocholesterol contributes to microglia-driven increases in astrocyte reactive oxygen species in a mouse model of Alzheimer's disease.Scientific reports · 2026Article
- Endothelial NOX4‑driven oxidative stress inhibition reverses HtrA1 deficiency‑induced blood‑brain barrier disruption and cognitive impairment.International journal of molecular medicine · 2026Article
- Endoplasmic Reticulum Stress: A Novel Target for the Prevention and Treatment of Hypertension and Its Related Diseases.Journal of cellular and molecular medicine · 2025Review
- Impact of Lipid Oxidation Products on Inflammation and Insulin Resistance: A Focus on Mechanisms of Action.Cell biochemistry and biophysics · 2025Review
- NOX4 Regulates NLRP3 by Inhibiting the Ubiquitination of LRRC8A to Promote Ferroptosis in Nucleus Pulposus Cells.Inflammation · 2025Article
- Lead (Pb) Induces Osteotoxicity Through the Activation of Mutually Reinforced ER Stress and ROS in MC3T3-E1 Cells.Biological trace element research · 2025Article
- Reactive oxygen species in hypertension.Nature reviews. Cardiology · 2025Review
- Delineating the NOX-Mediated Promising Therapeutic Strategies for the Management of Various Cardiovascular Disorders: A Comprehensive Review.Current vascular pharmacology · 2025Review
- Article
- The role of signaling pathways mediated by the GPCRs CysLTR1/2 in melanocyte proliferation and senescence.Science signaling · 2024Review
- Skeletal muscle-on-a-chip in microgravity as a platform for regeneration modeling and drug screening.Stem cell reports · 2024Article
- IRE1α: from the function to the potential therapeutic target in atherosclerosis.Molecular and cellular biochemistry · 2024Review
- Cholestane-3β,5α,6β-triol Induces Multiple Cell Death in A549 Cells via ER Stress and Autophagy Activation.Marine drugs · 2024Article
- In Vitro Evaluation of the Effects of 7-Ketocholesterol and 7β-Hydroxycholesterol on the Peroxisomal Status: Prevention of Peroxisomal Damages and Concept of Pexotherapy.Advances in experimental medicine and biology · 2024Article
- Oxysterols in Vascular Cells and Role in Atherosclerosis.Advances in experimental medicine and biology · 2024Article
- Impact of Oxysterols in Age-Related Disorders and Strategies to Alleviate Adverse Effects.Advances in experimental medicine and biology · 2024Review
- Cytoprotective effects of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol on 7-ketocholesterol - Induced oxiapoptophagy: Major roles of PI3-K / PDK-1 / Akt signaling pathway and glutathione peroxidase activity in cell rescue.Current research in toxicology · 2024Article
- Association of Serum Levels of Cholesterol Absorption and Synthesis Markers with the Presence of Cardiovascular Disease: The CACHE Study CVD Analysis.Journal of atherosclerosis and thrombosis · 2023Article
- The Unfolded Protein Response: A Double-Edged Sword for Brain Health.Antioxidants (Basel, Switzerland) · 2023Review
- Identification of 7-Ketocholesterol-Modulated Pathways and Sterculic Acid Protective Effect in Retinal Pigmented Epithelium Cells by Using Genome-Wide Transcriptomic Analysis.International journal of molecular sciences · 2023Article
138 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms involved in the cytotoxic action of oxysterols in the pathogenesis of atherosclerosis still remain poorly understood. Among the major oxysterols present in oxidized low-density lipoprotein, we show here that 7-ketocholesterol (7-Kchol) induces oxidative stress and/or apoptotic events in human aortic smooth muscle cells (SMCs). This specific effect of 7-Kchol is mediated by a robust upregulation (threefold from the basal level) of Nox-4, a reactive oxygen species (ROS)-generating NAD(P)H oxidase homologue. This effect was highlighted by silencing Nox-4 expression with a specific small interfering RNA, which significantly reduced the 7-Kchol-induced production of ROS and abolished apoptotic events. Furthermore, the 7-Kchol activating pathway included an early triggering of endoplasmic reticulum stress, as assessed by transient intracellular Ca(2+) oscillations, and the induction of the expression of the cell death effector CHOP and of GRP78/Bip chaperone via the activation of IRE-1, all hallmarks of the unfolded protein response (UPR). We also showed that 7-Kchol activated the IRE-1/Jun-NH(2)-terminal kinase (JNK)/AP-1 signaling pathway to promote Nox-4 expression. Silencing of IRE-1 and JNK inhibition downregulated Nox-4 expression and subsequently prevented the UPR-dependent cell death induced by 7-Kchol. These findings demonstrate that Nox-4 plays a key role in 7-Kchol-induced SMC death, which is consistent with the hypothesis that Nox-4/oxysterols are involved in the pathogenesis of atherosclerosis.
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