ArticleToxicological sciences : an official journal of the Society of Toxicology2009
Metal ions-stimulated iron oxidation in hydroxylases facilitates stabilization of HIF-1 alpha protein.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- Human bone marrow-mesenchymal stem cells differentiation into brain-like endothelial cells.Turkish journal of biology = Turk biyoloji dergisi · 2026Article
- Mechanistic Investigation of Adociaquinone and Xestoquinone Derivatives in Breast Cancer Cells.Marine drugs · 2025Article
- Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.Journal of medicinal chemistry · 2025Review
- Plants' molecular behavior to heavy metals: from criticality to toxicity.Frontiers in plant science · 2024Review
- Single-cell RNA sequencing reveals differences between force application and bearing in ankle cartilage.Cell biology and toxicology · 2023Article
- Renal hypoxia-HIF-PHD-EPO signaling in transition metal nephrotoxicity: friend or foe?Archives of toxicology · 2022Review
- Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment.Cancers · 2022Review
- Hypoxia Promotes Neutrophil Survival After Acute Myocardial Infarction.Frontiers in immunology · 2022Article
- Single-cell RNA sequence presents atlas analysis for chondrocytes in the talus and reveals the potential mechanism in coping with mechanical stress.Frontiers in cell and developmental biology · 2022Article
- Dual effects of hypoxia on proliferation and osteogenic differentiation of mouse clonal mesenchymal stem cells.Bioprocess and biosystems engineering · 2021Article
- THE MAIN CYTOTOXIC EFFECTS OF METHYLSELENINIC ACID ON VARIOUS CANCER CELLS.International journal of molecular sciences · 2021Review
- Interplay among miR-29 family, mineral metabolism, and gene regulation in Bos indicus muscle.Molecular genetics and genomics : MGG · 2020Article
- The small members of the JMJD protein family: Enzymatic jewels or jinxes?Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Zinc ion dyshomeostasis increases resistance of prostate cancer cells to oxidative stress via upregulation of HIF1α.Oncotarget · 2018Article
- Potential Mechanisms of Action for Vitamin C in Cancer: Reviewing the Evidence.Frontiers in physiology · 2018Review
- Expression of hypoxia inducible factor 1α and 2α and its association with vitamin C level in thyroid lesions.Journal of biomedical science · 2017Article
- Ni induces the CRR1-dependent regulon revealing overlap and distinction between hypoxia and Cu deficiency responses in Chlamydomonas reinhardtii.Metallomics : integrated biometal science · 2016Article
- Ascorbate as a co-factor for fe- and 2-oxoglutarate dependent dioxygenases: physiological activity in tumor growth and progression.Frontiers in oncology · 2014Review
- Tungsten carbide cobalt nanoparticles exert hypoxia-like effects on the gene expression level in human keratinocytes.BMC genomics · 2010Article
- Increased prolyl 4-hydroxylase expression and differential regulation of hypoxia-inducible factors in the aged rat brain.American journal of physiology. Regulatory, integrative and comparative physiology · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The exposure of cells to several metal ions stabilizes HIF-1 alpha protein. However, the molecular mechanisms are not completely understood. They may involve inhibition of hydroxylation by either substitution of iron by metal ions or by iron oxidation in the hydroxylases. Here we provide evidence supporting the latter mechanism. We show that HIF-1 alpha stabilization in human lung epithelial cells occurred following exposure to various metal and metalloid ions, including those that cannot substitute for iron in the hydroxylases. In each case addition of the reducing agent ascorbic acid (AA)* abolished HIF-1 alpha protein stabilization. To better understand the role of iron oxidation in hydroxylase inhibition and to define the role of AA in the enzyme recovery we applied molecular modeling techniques. Our results indicate that the energy required for iron substitution by Ni(II) in the enzyme is high and unlikely to be achieved in a biological system. Additionally, computer modeling allowed us to identify a tridentate coordination of AA with the enzyme-bound iron, which explains the specific demand for AA as the iron reductant. Thus, the stabilization of HIF-1 alpha by numerous metal ions that cannot substitute for iron in the enzyme, the alleviation of this effect by AA, and our computer modeling data support the hypothesis of iron oxidation in the hydroxylases following exposure to metal ions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.