ArticleCellular signalling2014
Distinct regulatory mechanisms of the human ferritin gene by hypoxia and hypoxia mimetic cobalt chloride at the transcriptional and post-transcriptional levels.
Article in Cellular signalling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Dynamic Regulation of Ferroptosis in a Neonatal Rat Model of Postnatal Hypoxia-Induced Acute Kidney Injury.Antioxidants (Basel, Switzerland) · 2026Article
- Modelling the monstrosities: experimental and computational systems for studying polyploid giant cancer cells.Expert reviews in molecular medicine · 2025Review
- Ferritin as an Effective Prognostic Factor and Potential Cancer Biomarker.Current issues in molecular biology · 2025Review
- Ferroptosis: a new promising target for hepatocellular carcinoma therapy.Molecular and cellular biochemistry · 2024Review
- Transcriptomics pave the way into mechanisms of cobalt and nickel toxicity: Nrf2-mediated cellular responses in liver carcinoma cells.Redox biology · 2024Article
- From ferroptosis to cuproptosis, and calcicoptosis, to find more novel metals-mediated distinct form of regulated cell death.Apoptosis : an international journal on programmed cell death · 2024Review
- A novel view of ferritin in cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Article
- The critical role and molecular mechanisms of ferroptosis in antioxidant systems: a narrative review.Annals of translational medicine · 2022Review
- Effect of 8-Day Fasting on Leukocytes Expression of Genes and Proteins Involved in Iron Metabolism in Healthy Men.International journal of molecular sciences · 2021Article
- Biochemistry of mammalian ferritins in the regulation of cellular iron homeostasis and oxidative responses.Science China. Life sciences · 2021Review
- Regulation of Ferroptosis Pathway by Ubiquitination.Frontiers in cell and developmental biology · 2021Review
- Ferroptosis is Involved in Hyperoxic Lung Injury in Neonatal Rats.Journal of inflammation research · 2021Article
- Article
- Ferroptosis: Final destination for cancer?Cell proliferation · 2020Review
- Dimerization of MORC2 through its C-terminal coiled-coil domain enhances chromatin dynamics and promotes DNA repair.Cell communication and signaling : CCS · 2019Article
- Carbonic anhydrase 9 confers resistance to ferroptosis/apoptosis in malignant mesothelioma under hypoxia.Redox biology · 2019Article
- Upregulation of fascin-1 is involved in HIF-1α-dependent invasion and migration of hypopharyngeal squamous cell carcinoma.International journal of oncology · 2019Article
- Impact of different methods of induction of cellular hypoxia: focus on protein homeostasis signaling pathways and morphology of C2C12 skeletal muscle cells differentiated into myotubes.Journal of physiology and biochemistry · 2019Article
- Article
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Authors and funding
3 authors at 1 institution in 1 country.
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Abstract
Cobalt chloride has been used as a hypoxia mimetic because it stabilizes hypoxia inducible factor-1α (HIF1-α) and activates gene transcription through a hypoxia responsive element (HRE). However, differences between hypoxia and hypoxia mimetic cobalt chloride in gene regulation remain elusive. Expression of ferritin, the major iron storage protein, is regulated at the transcriptional and posttranscriptional levels through DNA and RNA regulatory elements. Here we demonstrate that hypoxia and cobalt chloride regulate ferritin heavy chain (ferritin H) expression by two distinct mechanisms. Both hypoxia and cobalt chloride increased HIF1-α but a putative HRE in the human ferritin H gene was not activated. Instead, cobalt chloride but not hypoxia activated ferritin H transcription through an antioxidant responsive element (ARE), to which Nrf2 was recruited. Intriguingly, cobalt chloride downregulated ferritin H protein expression while it upregulated other ARE-regulated antioxidant genes in K562 cells. Further characterization demonstrated that cobalt chloride increased interaction between iron regulatory proteins (IRP1 and IRP2) and iron responsive element (IRE) in the 5'UTR of ferritin H mRNA, resulting in translational block of the accumulated ferritin H mRNA. In contrast, hypoxia had marginal effect on ferritin H transcription but increased its translation through decreased IRP1-IRE interaction. These results suggest that hypoxia and hypoxia mimetic cobalt chloride employ distinct regulatory mechanisms through the interplay between DNA and mRNA elements at the transcriptional and post-transcriptional levels.
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Registered trials
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