Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Iron Metabolism and Toxicity
ijms-logo
Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Iron Metabolism and Toxicity

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 4605

Special Issue Editor

Prof. Dr. Jedrzej Antosiewicz

E-Mail Website
Guest Editor
Department of Bioenergetics and Physiology of Exercise, Faculty of Health Sciences, Medical University of Gdansk, 80-210 Gdansk, Poland
Interests: iron metabolism; ferritin; transferrin receptor; exercise; hepcidine; diseases; iron-dependent oxidative stress
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is difficult to find out a process in the human body that directly or indirectly is not dependent on iron among them are synthesis of DNA, RNA, cellular respiration, hormone synthesis, oxygen transport, and many others. Thus, proper iron status and metabolism are essential for our well- being in  adulthood and in healthy aging without disease. Despite its crucial role in human physiology iron is very toxic which is caused by its ability to participate in one-electron reactions. As the effect, it can stimulate the formation of toxic reactive oxygen species like hydroxyl radical, lipid peroxyl, and many others. Thus, iron metabolism is strictly controlled to minimize its toxicity. Special proteins are responsible for their transport, storage, delivering of metalo- proteins (iron chaperons). At the same time all of these proteins also protect the iron from uncontrolled participation in free radical’s chain formation reactions that lead to extremely disruptive effects. Besides, there are hormones like hepcidin, erytropherone, or erythropoietin which directly or indirectly control iron metabolism. Iron deficiency is the most common dietary deficit in the world however, in wealthy countries reverse situation is a fact and many people accumulate iron in their bodies and experienced iron-overload. Some studies show that such accumulation increases the risk of several diseases like heart attack, diabetes, cancer, and others. Iron metabolism seems to have a myriad of questions related to its toxicity that need to be answered. First of all, why do we accumulate too much iron, or what can we do to protect ourselves from this? Secondly, how iron toxicity affects different tissues for example if too much iron is accumulated in skeletal muscle or liver can it affect the functioning of the human heart or brain? If yes what is the mechanism and pathway of signaling? 

The idea of the current Special Issue Iron Metabolism and Toxicity is to offer the possibility of collecting high-quality publications and to provide an interdisciplinary approach by submitting original papers and updated reviews on various aspects of iron metabolism and its relation to the pathomechanism of several diseases like diabetes, cardiovascular, cancer, frailty, and many others. Furthermore, the identification of biochemical pathways is impaired by disease processes that are related to iron metabolism, or changes in iron metabolism induced by physiological stimuli like exercise, cryotherapy, is chemic preconditioning, etc. are awaited. 

Prof. Dr. Jedrzej Antosiewicz
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • iron metabolism
  • ferritin
  • transferrin receptor
  • hepcidine
  • iron-dependent oxidative stress
  • iron toxicity

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

13 pages, 2405 KiB  
Article
Using Biotinylated Iron-Responsive Element to Analyze the Activity of Iron Regulatory Proteins
by De-Liang Zhang, Hayden Ollivierre and Tracey A. Rouault
Int. J. Mol. Sci. 2024, 25(9), 4852; https://doi.org/10.3390/ijms25094852 - 29 Apr 2024
Viewed by 199
Abstract
Iron regulatory proteins (IRP1 and IRP2) are the master regulators of mammalian iron homeostasis. They bind to the iron-responsive elements (IREs) of the transcripts of iron-related genes to regulate their expression, thereby maintaining cellular iron availability. The primary method to measure the IRE-binding [...] Read more.
Iron regulatory proteins (IRP1 and IRP2) are the master regulators of mammalian iron homeostasis. They bind to the iron-responsive elements (IREs) of the transcripts of iron-related genes to regulate their expression, thereby maintaining cellular iron availability. The primary method to measure the IRE-binding activity of IRPs is the electrophoresis mobility shift assay (EMSA). This method is particularly useful for evaluating IRP1 activity, since IRP1 is a bifunctional enzyme and its protein levels remain similar during conversion between the IRE-binding protein and cytosolic aconitase forms. Here, we exploited a method of using a biotinylated-IRE probe to separate IRE-binding IRPs followed by immunoblotting to analyze the IRE-binding activity. This method allows for the successful measurement of IRP activity in cultured cells and mouse tissues under various iron conditions. By separating IRE-binding IRPs from the rest of the lysates, this method increases the specificity of IRP antibodies and verifies whether a band represents an IRP, thereby revealing some previously unrecognized information about IRPs. With this method, we showed that the S711-phosphorylated IRP1 was found only in the IRE-binding form in PMA-treated Hep3B cells. Second, we found a truncated IRE-binding IRP2 isoform that is generated by proteolytic cleavage on sites in the 73aa insert region of the IRP2 protein. Third, we found that higher levels of SDS, compared to 1–2% SDS in regular loading buffer, could dramatically increase the band intensity of IRPs in immunoblots, especially in HL-60 cells. Fourth, we found that the addition of SDS or LDS to cell lysates activated protein degradation at 37 °C or room temperature, especially in HL-60 cell lysates. As this method is more practical, sensitive, and cost-effective, we believe that its application will enhance future research on iron regulation and metabolism. Full article
(This article belongs to the Special Issue Iron Metabolism and Toxicity)
►▼ Show Figures

Figure 1

20 pages, 14537 KiB  
Article
Identification of AURKA as a Biomarker Associated with Cuproptosis and Ferroptosis in HNSCC
by Xiao Jia, Jiao Tian, Yueyue Fu, Yiqi Wang, Yang Yang, Mengzhou Zhang, Cheng Yang and Yijin Liu
Int. J. Mol. Sci. 2024, 25(8), 4372; https://doi.org/10.3390/ijms25084372 - 16 Apr 2024
Viewed by 476
Abstract
Cuproptosis and ferroptosis represent copper- and iron-dependent forms of cell death, respectively, and both are known to play pivotal roles in head and neck squamous cell carcinoma (HNSCC). However, few studies have explored the prognostic signatures related to cuproptosis and ferroptosis in HNSCC. [...] Read more.
Cuproptosis and ferroptosis represent copper- and iron-dependent forms of cell death, respectively, and both are known to play pivotal roles in head and neck squamous cell carcinoma (HNSCC). However, few studies have explored the prognostic signatures related to cuproptosis and ferroptosis in HNSCC. Our objective was to construct a prognostic model based on genes associated with cuproptosis and ferroptosis. We randomly assigned 502 HSNCC samples from The Cancer Genome Atlas (TCGA) into training and testing sets. Pearson correlation analysis was utilized to identify cuproptosis-associated ferroptosis genes in the training set. Cox proportional hazards (COX) regression and least absolute shrinkage operator (LASSO) were employed to construct the prognostic model. The performance of the prognostic model was internally validated using single-factor COX regression, multifactor COX regression, Kaplan–Meier analysis, principal component analysis (PCA), and receiver operating curve (ROC) analysis. Additionally, we obtained 97 samples from the Gene Expression Omnibus (GEO) database for external validation. The constructed model, based on 12 cuproptosis-associated ferroptosis genes, proved to be an independent predictor of HNSCC prognosis. Among these genes, the increased expression of aurora kinase A (AURKA) has been implicated in various cancers. To further investigate, we employed small interfering RNAs (siRNAs) to knock down AURKA expression and conducted functional experiments. The results demonstrated that AURKA knockdown significantly inhibited the proliferation and migration of HNSCC cells (Cal27 and CNE2). Therefore, AURKA may serve as a potential biomarker in HNSCC. Full article
(This article belongs to the Special Issue Iron Metabolism and Toxicity)
►▼ Show Figures

Figure 1

15 pages, 1266 KiB  
Article
The Effect of a Six-Week Nordic Walking Training Cycle on Oxidative Damage of Macromolecules and Iron Metabolism in Older Patients with Multiple Myeloma in Remission—Randomized Clinical Trial
by Olga Czerwińska-Ledwig, Artur Jurczyszyn, Anna Piotrowska, Wanda Pilch, Jędrzej Antosiewicz and Małgorzata Żychowska
Int. J. Mol. Sci. 2023, 24(20), 15358; https://doi.org/10.3390/ijms242015358 - 19 Oct 2023
Viewed by 1107
Abstract
Multiple myeloma (MM) is an incurable hematologic malignancy originating from clonal plasma cell proliferation within the bone marrow, predominantly affecting older individuals. While anemia serves as a diagnostic criterion for MM, it often ameliorates upon achieving disease remission. Iron metabolism parameters have emerged [...] Read more.
Multiple myeloma (MM) is an incurable hematologic malignancy originating from clonal plasma cell proliferation within the bone marrow, predominantly affecting older individuals. While anemia serves as a diagnostic criterion for MM, it often ameliorates upon achieving disease remission. Iron metabolism parameters have emerged as potential prognostic indicators in MM. Notably, physical exercise has been established to influence iron metabolism. This study aimed to assess alterations in serum iron, ferritin, and transferrin concentrations, as well as leukocyte gene expression, in MM patients undergoing a six-week cycle of Nordic walking training. Thirty patients divided into an exercise group (NW, n = 15, mean age 63.1 ± 8.4 years) and a control group (CG, n = 15, mean age: 63.5 ± 3.6 years) completed the study protocol. Blood samples were collected at baseline, after three and six weeks of training, and after nine weeks. Serum ferritin, transferrin, and iron concentrations were measured, along with the leukocyte expression of genes. Additionally, serum oxidative damage marker levels were determined. Following the Nordic walking training cycle, a declining trend in serum ferritin concentrations was observed. Intracellular mRNA levels of genes associated with iron metabolism were positively influenced by the training regimen, indicating the potential impact of this physical activity on gene expression and ferritin concentrations. Although positive trends were noted, extended training periods might be requisite for significant changes. To conclude, moderate-intensity exercise induces favorable shifts in the analyzed parameters among MM patients, potentially influencing disease progression. Consequently, Nordic walking training is a safe recommendation for MM patients, though sustained training beyond six weeks could be necessary for notable effects on iron metabolism factors. Full article
(This article belongs to the Special Issue Iron Metabolism and Toxicity)
►▼ Show Figures

Figure 1

20 pages, 6120 KiB  
Article
Pseudomonas aeruginosa Dps (PA0962) Functions in H2O2 Mediated Oxidative Stress Defense and Exhibits In Vitro DNA Cleaving Activity
by Nimesha Rajapaksha, Anabel Soldano, Huili Yao, Fabrizio Donnarumma, Maithri M. Kashipathy, Steve Seibold, Kevin P. Battaile, Scott Lovell and Mario Rivera
Int. J. Mol. Sci. 2023, 24(5), 4669; https://doi.org/10.3390/ijms24054669 - 28 Feb 2023
Cited by 2 | Viewed by 2375
Abstract
We report the structural, biochemical, and functional characterization of the product of gene PA0962 from Pseudomonas aeruginosa PAO1. The protein, termed Pa Dps, adopts the Dps subunit fold and oligomerizes into a nearly spherical 12-mer quaternary structure at pH 6.0 or in the [...] Read more.
We report the structural, biochemical, and functional characterization of the product of gene PA0962 from Pseudomonas aeruginosa PAO1. The protein, termed Pa Dps, adopts the Dps subunit fold and oligomerizes into a nearly spherical 12-mer quaternary structure at pH 6.0 or in the presence of divalent cations at neutral pH and above. The 12-Mer Pa Dps contains two di-iron centers at the interface of each subunit dimer, coordinated by conserved His, Glu, and Asp residues. In vitro, the di-iron centers catalyze the oxidation of Fe2+ utilizing H2O2 (not O2) as an oxidant, suggesting Pa Dps functions to aid P. aeruginosa to survive H2O2-mediated oxidative stress. In agreement, a P. aeruginosa Δdps mutant is significantly more susceptible to H2O2 than the parent strain. The Pa Dps structure harbors a novel network of Tyr residues at the interface of each subunit dimer between the two di-iron centers, which captures radicals generated during Fe2+ oxidation at the ferroxidase centers and forms di-tyrosine linkages, thus effectively trapping the radicals within the Dps shell. Surprisingly, incubating Pa Dps and DNA revealed unprecedented DNA cleaving activity that is independent of H2O2 or O2 but requires divalent cations and 12-mer Pa Dps. Full article
(This article belongs to the Special Issue Iron Metabolism and Toxicity)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop