ArticleApoptosis : an international journal on programmed cell death2021
High-dose copper activates p53-independent apoptosis through the induction of nucleolar stress in human cell lines.
Article in Apoptosis : an international journal on programmed cell death, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Copper homeostasis and cuproptosis: molecular mechanisms and therapeutic opportunities.Molecular biomedicine · 2026Review
- The molecular mechanism and therapeutic landscape of copper and cuproptosis in cancer.Signal transduction and targeted therapy · 2025Review
- Copper in cancer: friend or foe? Metabolism, dysregulation, and therapeutic opportunities.Cancer communications (London, England) · 2025Review
- AKT1 Phosphorylates FDX1 to Promote Cuproptosis Resistance in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cuproptosis and its potential role in musculoskeletal disease.Frontiers in cell and developmental biology · 2025Review
- Deciphering the Role of Copper Homeostasis in Atherosclerosis: From Molecular Mechanisms to Therapeutic Targets.International journal of molecular sciences · 2024Review
- Don´t give up on mitochondria as a target for the treatment of diabetes and its complications.World journal of diabetes · 2024Article
- Exploring the Sublethal Impacts of Cu and Zn on Daphnia magna: a transcriptomic perspective.BMC genomics · 2024Article
- Mechanisms of cuproptosis and its relevance to distinct diseases.Apoptosis : an international journal on programmed cell death · 2024Review
- Exploring Copper's role in stroke: progress and treatment approaches.Frontiers in pharmacology · 2024Review
- Elesclomol, a copper-transporting therapeutic agent targeting mitochondria: from discovery to its novel applications.Journal of translational medicine · 2023Review
- Abnormalities in Copper Status Associated with an Elevated Risk of Parkinson's Phenotype Development.Antioxidants (Basel, Switzerland) · 2023Review
- Copper metabolism in cell death and autophagy.Autophagy · 2023Review
- Development of a cuproptosis-related signature for prognosis prediction in lung adenocarcinoma based on WGCNA.Translational lung cancer research · 2023Article
- Bioinformatics-Based Analysis of Key Genes in Steroid-Induced Osteonecrosis of the Femoral Head That Are Associated with Copper Metabolism.Biomedicines · 2023Article
- A cuproptosis-related lncRNA signature identified prognosis and tumour immune microenvironment in kidney renal clear cell carcinoma.Frontiers in molecular biosciences · 2022Article
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Authors and funding
4 authors at 2 institutions in 1 country.
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Abstract
Copper is an essential micronutrient involved in many redox reactions in human cells. However, a high concentration of copper, intake from the environment or abnormal accumulation within cells because of genetic mutation, leads to cell toxicity. This is attributable to oxidative damage, altered gene expression, and functional impairment of the mitochondria. Copper stress also alters the morphology of the nucleolus, but the process has not been fully elucidated. In this study, cells were treated with copper sulfate at 3-9 ppm and examined if a high dose of copper would block ribosome biogenesis. With the incorrect distribution of nucleolar proteins nucleophosmin and fibrillarin to the nucleoplasm, ribosomal RNA (rRNA) processing was impaired; 34S rRNA from an abnormal A2 cut increased, and downstream pre-rRNAs decreased. The under-accumulation of 60S subunits was detected using sucrose gradients. From transcriptome analysis, ribosome synthesis-related genes were misregulated. Blockage in ribosome synthesis under copper-treatment induced nucleolar stress and triggered p53-independent apoptosis pathways. Thus, nucleolar stress is one cause of cell death under copper exposure.
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