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Zinc and Manganese in Human Health and Disease
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Zinc and Manganese in Human Health and Disease

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

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 7010

Special Issue Editor

Dr. Julian Markovich Rozenberg

E-Mail Website
Guest Editor
Moscow Institute of Physics and Technology, National Research University, 141700 Moscow, Russia
Interests: transcriptional regulation; gene isoform; transcription (linguistics); gene expression; zinc finger

Special Issue Information

Dear Colleagues, 

Metal ion homeostasis is fundamental for life. Specifically, transition metals iron, manganese, and zinc play a pivotal role in mitochondrial metabolism and energy generation, anti-oxidation defense, transcriptional regulation, and the immune response. The misregulation of expression or mutations in ion carriers and the corresponding changes in Mn2+ and Zn2+ levels suggest that these ions play a pivotal role in cancer progression. Coordinated changes in Mn2+ and Zn2+ ion carriers have been detected in cancers, suggesting that particular mechanisms influenced by both ions might be required for the growth of cancer cells, metastasis, and immune evasion.

Mechanistically, Zn and Mn effects converge on mitochondria-induced apoptosis, transcriptional regulation, and immune response regulation by the cGAS-STING signaling pathway. Both Zn and Mn influence cancer progression and impact treatment efficacy in animal models and clinical trials. 

In this Special Issue, we invite papers covering all aspects of Zn- and Mn-related biology, such as development of biosensors, enzyme kinetics, drug development including nanomaterials, biomarker research, and clinical applications, interaction with other transition metals (such as Fe and Mg), and Ca and Mg homeostasis and signaling.

Dr. Julian Markovich Rozenberg
Guest Editor

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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.

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Keywords

  • metal ion homeostasis and signaling
  • Zn
  • Mn
  • Zn2+
  • Mn2+
  • mitochondrial metabolism
  • energy generation
  • anti-oxidation defense
  • transcriptional regulation
  • immune response
  • biosensors
  • enzyme kinetics
  • drug development
  • biomarker research
  • clinical application
  • interaction with other transition metals

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Published Papers (4 papers)

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Research

18 pages, 3889 KiB  
Article
Cardiotoxicity of Iron and Zinc and Their Association with the Mitochondrial Unfolded Protein Response in Humans
by Vid Mirosevic, Tomo Svagusa, Natalija Matic, Kresimir Maldini, Mario Siljeg, Davor Milicic, Hrvoje Gasparovic, Igor Rudez, Ana Sepac, Lucija Gojmerac, Ana Kulic, Petra Bakovic and Filip Sedlic
Int. J. Mol. Sci. 2024, 25(17), 9648; https://doi.org/10.3390/ijms25179648 - 6 Sep 2024
Viewed by 510
Abstract
This study was designed to examine the association between myocardial concentrations of the trace elements Cu, Fe, Mn, Mo, and Zn and the expression of mitochondrial unfolded protein response (UPRmt) elements and the age of patients who received heart transplantation or a left-ventricular [...] Read more.
This study was designed to examine the association between myocardial concentrations of the trace elements Cu, Fe, Mn, Mo, and Zn and the expression of mitochondrial unfolded protein response (UPRmt) elements and the age of patients who received heart transplantation or a left-ventricular assist device (ageHTx/LVAD). Inductively coupled plasma mass spectrometry was used to determine the concentration of Cu, Fe, Mn, Mo, and Zn in the myocardium of control subjects and patients undergoing heart transplantation or left-ventricular assist device (LVAD) implantation. We used ELISA to quantify the expression of UPRmt proteins and 4-Hydroxynonenal (4-HNE), which served as a marker of oxidative-stress-induced lipid peroxidation. Concentrations of Cu, Mn, Mo, and Zn were similar in the control and heart failure (HF) myocardium, while Fe showed a significant decrease in the HF group compared to the control. A higher cumulative concentration of Fe and Zn in the myocardium was associated with reduced ageHTx/LVAD, which was not observed for other combinations of trace elements or their individual effects. The trace elements Cu, Mn, and Zn showed positive correlations with several UPRmt proteins, while Fe had a negative correlation with UPRmt effector protease YME1L. None of the trace elements correlated with 4-HNE in the myocardium. The concentrations of the trace elements Mn and Zn were significantly higher in the myocardium of patients with dilated cardiomyopathy than in patients with ischemic cardiomyopathy. A higher cumulative concentration of Fe and Zn in the myocardium was associated with a younger age at which patients received heart transplantation or LVAD, potentially suggesting an acceleration of HF. A positive correlation between myocardial Cu, Mn, and Zn and the expression of UPRmt proteins and a negative correlation between myocardial Fe and YME1L expression suggest that these trace elements exerted their actions on the human heart by interacting with the UPRmt. An altered generation of oxidative stress was not an underlying mechanism of the observed changes. Full article
(This article belongs to the Special Issue Zinc and Manganese in Human Health and Disease)
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19 pages, 3413 KiB  
Article
Effects of Superficial Scratching and Engineered Nanomaterials on Skin Gene Profiles and Microbiota in SKH-1 Mice
by Kuunsäde Mäenpää, Marit Ilves, Lan Zhao, Harri Alenius, Hanna Sinkko and Piia Karisola
Int. J. Mol. Sci. 2023, 24(21), 15629; https://doi.org/10.3390/ijms242115629 - 26 Oct 2023
Cited by 1 | Viewed by 1400
Abstract
Scratching damages upper layers of the skin, breaks this first line of immune defence, and leads to inflammation response, which often also modifies the microbiota of the skin. Although the healing of incision wounds is well-described, there are fewer studies on superficial wounds. [...] Read more.
Scratching damages upper layers of the skin, breaks this first line of immune defence, and leads to inflammation response, which often also modifies the microbiota of the skin. Although the healing of incision wounds is well-described, there are fewer studies on superficial wounds. We used a simulated model of skin scratching to study changes in the host transcriptome, skin microbiota, and their relationship. Additionally, we examined the effect of nanosized ZnO, TiO2, and Ag on both intact and damaged skin. At 24 h after exposure, the number of neutrophils was increased, 396 genes were differentially expressed, and microbiota compositions changed between scratched and intact control skin. At 7 d, the skin was still colonised by gut-associated microbes, including Lachnospiraceae, present in the cage environment, while the transcriptomic responses decreased. To sum up, the nanomaterial exposures reduced the relative abundance of cutaneous microbes on healthy skin, but the effect of scratching was more significant for the transcriptome than the nanomaterial exposure both at 24 h and 7 d. We conclude that superficial skin scratching induces inflammatory cell accumulation and changes in gene expression especially at 24 h, while the changes in the microbiota last at least 7 days. Full article
(This article belongs to the Special Issue Zinc and Manganese in Human Health and Disease)
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14 pages, 38637 KiB  
Article
Inhibitory Effect of Zinc on Colorectal Cancer by Granzyme B Transcriptional Regulation in Cytotoxic T Cells
by Naoya Nakagawa, Yutaka Fujisawa, Huihui Xiang, Hidemitsu Kitamura and Keigo Nishida
Int. J. Mol. Sci. 2023, 24(11), 9457; https://doi.org/10.3390/ijms24119457 - 29 May 2023
Cited by 2 | Viewed by 2451
Abstract
Zinc is one of the essential trace elements and is involved in various functions in the body. Zinc deficiency is known to cause immune abnormalities, but the mechanism is not fully understood. Therefore, we focused our research on tumor immunity to elucidate the [...] Read more.
Zinc is one of the essential trace elements and is involved in various functions in the body. Zinc deficiency is known to cause immune abnormalities, but the mechanism is not fully understood. Therefore, we focused our research on tumor immunity to elucidate the effect of zinc on colorectal cancer and its mechanisms. Mice were treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) to develop colorectal cancer, and the relationship between zinc content in the diet and the number and area of tumors in the colon was observed. The number of tumors in the colon was significantly higher in the no-zinc-added group than in the normal zinc intake group, and about half as many in the high-zinc-intake group as in the normal-zinc-intake group. In T-cell-deficient mice, the number of tumors in the high-zinc-intake group was similar to that in the normal-zinc-intake group, suggesting that the inhibitory effect of zinc was dependent on T cells. Furthermore, we found that the amount of granzyme B transcript released by cytotoxic T cells upon antigen stimulation was significantly increased by the addition of zinc. We also showed that granzyme B transcriptional activation by zinc addition was dependent on calcineurin activity. In this study, we have shown that zinc exerts its tumor-suppressive effect by acting on cytotoxic T cells, the center of cellular immunity, and increases the transcription of granzyme B, one of the key molecules in tumor immunity. Full article
(This article belongs to the Special Issue Zinc and Manganese in Human Health and Disease)
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12 pages, 2885 KiB  
Article
The Regulation of ZIP8 by Dietary Manganese in Mice
by Suetmui Yu and Ningning Zhao
Int. J. Mol. Sci. 2023, 24(6), 5962; https://doi.org/10.3390/ijms24065962 - 22 Mar 2023
Cited by 3 | Viewed by 1957
Abstract
ZIP8 is a newly identified manganese transporter. A lack of functional ZIP8 results in severe manganese deficiency in both humans and mice, indicating that ZIP8 plays a crucial role in maintaining body manganese homeostasis. Despite a well-acknowledged connection between ZIP8 and manganese metabolism, [...] Read more.
ZIP8 is a newly identified manganese transporter. A lack of functional ZIP8 results in severe manganese deficiency in both humans and mice, indicating that ZIP8 plays a crucial role in maintaining body manganese homeostasis. Despite a well-acknowledged connection between ZIP8 and manganese metabolism, how ZIP8 is regulated under high-manganese conditions remains unclear. The primary goal of this study was to examine the regulation of ZIP8 by high-manganese intake. We used both neonatal and adult mouse models in which mice were supplied with dietary sources containing either a normal or a high level of manganese. We discovered that high-manganese intake caused a reduction in liver ZIP8 protein in young mice. Since a decrease in hepatic ZIP8 leads to reduced manganese reabsorption from the bile, our study identified a novel mechanism for the regulation of manganese homeostasis under high-manganese conditions: high dietary manganese intake results in a decrease in ZIP8 in the liver, which in turn decreases the reabsorption of manganese from the bile to prevent manganese overload in the liver. Interestingly, we found that a high-manganese diet did not cause a decrease in hepatic ZIP8 in adult animals. To determine the potential reason for this age-dependent variation, we compared the expressions of liver ZIP8 in 3-week-old and 12-week-old mice. We found that liver ZIP8 protein content in 12-week-old mice decreases when compared with that of 3-week-old mice under normal conditions. Overall, results from this study provide novel insights to facilitate the understanding of ZIP8’s function in regulating manganese metabolism. Full article
(This article belongs to the Special Issue Zinc and Manganese in Human Health and Disease)
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