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The Role of Mg Homeostasis in 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: 15 April 2024 | Viewed by 8988

Special Issue Editor

Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida (IRBLleida), Arnau de Vilanova University Hospital, 25198 Lleida, Spain
Interests: bone disease; mineral metabolism; renal disease; vascular calcification; calcium-sensing receptor; fibroblast growth factor 23; sclerostin; vitamin D; parathyroid hormone

Special Issue Information

Dear Colleagues, 

Magnesium is the fourth most abundant mineral in the body, with the vast majority of it being stored in bone. Maintaining adequate magnesium levels is key to health. In this regard, hypomagnesemia has been related to diseases such as osteoporosis or cardiovascular diseases and has also been associated with mortality. At the molecular level, magnesium is capable of modulating membrane receptors such as the transient receptor potential melastatin-subfamily member 7 (TRPM7) or the calcium-sensing receptor (CaSR), regulating signaling pathways involved in many cellular functions such as cell differentiation, proliferation, inflammation, etc.

The aim of this Special Issue is to compile the latest scientific advances on the role of magnesium homeostasis in disease, such as kidney disease, diabetes, osteoporosis, genetic diseases, cardiovascular disease, and cancer, among others. In addition, the role of magnesium in the control of cellular processes such as oxidative stress or inflammation will also be discussed.

Dr. Juan Miguel Diaz-Tocados
Guest Editor

Manuscript Submission Information

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Keywords

  • magnesium
  • chronic diseases
  • diabetes
  • bone disease
  • mineral metabolism
  • renal disease
  • inflammation
  • cardiovascular disease

Published Papers (7 papers)

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Research

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18 pages, 3671 KiB  
Article
Evaluating Serum Calcium and Magnesium Levels as Predictive Biomarkers for Tuberculosis and COVID-19 Severity: A Romanian Prospective Study
by Ramona Cioboata, Corina Maria Vasile, Mara Amalia Bălteanu, Dragos Eugen Georgescu, Claudia Toma, Amelia Sanda Dracea and Dragos Nicolosu
Int. J. Mol. Sci. 2024, 25(1), 418; https://doi.org/10.3390/ijms25010418 - 28 Dec 2023
Viewed by 641
Abstract
In Romania, the highest incidence of tuberculosis (TB) within the European Union was reported in 2020, highlighting a significant health challenge. This is compounded by the COVID-19 pandemic, which has severely impacted healthcare services, including TB management. Both TB and COVID-19, diseases with [...] Read more.
In Romania, the highest incidence of tuberculosis (TB) within the European Union was reported in 2020, highlighting a significant health challenge. This is compounded by the COVID-19 pandemic, which has severely impacted healthcare services, including TB management. Both TB and COVID-19, diseases with considerable morbidity and mortality, have shown potential links to electrolyte imbalances. We conducted a prospective study at Victor Babes Hospital, Romania on 146 patients (74 with TB, 72 with COVID-19) between December 2021 and July 2023. This study assessed correlations between disease severity and serum calcium and magnesium levels, as well as pulmonary function. Adult patients with confirmed diagnoses and comprehensive medical records were included, excluding those with chronic respiratory diseases or unrelated electrolyte imbalances. Statistical analysis utilized the Kruskal–Wallis test and Dunn’s procedure for non-normally distributed data. Low serum calcium and magnesium levels were significantly correlated with severe forms of TB and COVID-19, suggesting their potential as biomarkers of disease progression. Patients with more severe TB (i.e., multiple cavities) exhibited significantly lower serum calcium (p = 0.0049) and magnesium levels (p = 0.0004). ROC analysis revealed high AUC values for serum calcium and serum magnesium in predicting COVID-19 severity, indicating their potential as biomarkers. This study demonstrates a significant association between lower serum calcium and magnesium levels and increased TB severity. Similarly, these electrolytes show promise as predictive markers for COVID-19 severity. These findings could serve as biomarkers for predicting the severity of TB and COVID-19, offering potential utility in clinical decision-making. Full article
(This article belongs to the Special Issue The Role of Mg Homeostasis in Disease)
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15 pages, 1641 KiB  
Article
Serum Mg Isotopic Composition Reveals That Mg Dyshomeostasis Remains in Type 1 Diabetes despite the Resolution of Hypomagnesemia
by Kaj Vaughan Sullivan, Yasmina Assantuh, Rosa Grigoryan, Marta Costas-Rodríguez, Eduardo Bolea-Fernandez, Bruno Lapauw, Steven Van Laecke and Frank Vanhaecke
Int. J. Mol. Sci. 2023, 24(21), 15683; https://doi.org/10.3390/ijms242115683 - 27 Oct 2023
Viewed by 833
Abstract
Hypomagnesemia was historically prevalent in individuals with type 1 diabetes mellitus (T1DM), but contemporary results indicate an incidence comparable to that in the general population, likely due to improved treatment in recent decades, resulting in better glycemic control. However, a recent study found [...] Read more.
Hypomagnesemia was historically prevalent in individuals with type 1 diabetes mellitus (T1DM), but contemporary results indicate an incidence comparable to that in the general population, likely due to improved treatment in recent decades, resulting in better glycemic control. However, a recent study found a significant difference between the serum Mg isotopic composition of T1DM individuals and controls, indicating that disruptions to Mg homeostasis persist. Significant deviations were also found in samples taken one year apart. To investigate whether the temporal variability in serum Mg isotopic composition is linked to the transient impact of administered insulin, Mg isotope ratios were determined in serum from 15 T1DM individuals before and one hour after insulin injection/meal consumption using multi-collector inductively coupled plasma-mass spectrometry. Consistent with results of the previous study, significant difference in the serum Mg isotopic composition was found between T1DM individuals and 10 sex-matched controls. However, the average difference between pre- and post-insulin injection/meal T1DM samples of 0.05 ± 0.13‰ (1SD) was not significant. No difference was observed for controls before (−0.12 ± 0.16‰) and after the meal (−0.10 ± 0.13‰) either, suggesting a lack of a postprandial Mg isotopic response within one hour of food consumption, and that the timing of the most recent meal may not require controlling for when determining serum Mg isotopic composition. Full article
(This article belongs to the Special Issue The Role of Mg Homeostasis in Disease)
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12 pages, 268 KiB  
Article
Metabolic Syndrome in Aging Men as a Factor Affecting the Relationship between Mg, Ca, and P in Serum and Bone
by Aleksandra Rył, Żaneta Ciosek, Aleksandra Szylińska, Alina Jurewicz, Andrzej Bohatyrewicz, Paweł Ziętek and Iwona Rotter
Int. J. Mol. Sci. 2023, 24(13), 10947; https://doi.org/10.3390/ijms241310947 - 30 Jun 2023
Cited by 1 | Viewed by 864
Abstract
The objective of this study was to evaluate the relationship between the prevalence of metabolic syndrome (MetS) and selected hormonal disorders and concentrations of magnesium (Mg), calcium (Ca), and phosphorus (P) in both blood serum and bone tissue. This study involved 152 men [...] Read more.
The objective of this study was to evaluate the relationship between the prevalence of metabolic syndrome (MetS) and selected hormonal disorders and concentrations of magnesium (Mg), calcium (Ca), and phosphorus (P) in both blood serum and bone tissue. This study involved 152 men with and without MetS. In the blood of the patients we examined, we determined levels of: testosterone (TT), estradiol (E2), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), insulin (I), osteocalcin (OC), and concentrations of markers of bone turnover. The concentration of Mg, Ca, and P was determined in the serum and bone tissue. In patients with MetS, the serum Ca concentration correlated with procollagen type I N-terminal propeptide (PINP) and parathyroid hormone (PTH). Among patients without MetS, the serum Ca concentration correlated with SHBG and OC, while Ca concentration in bone correlated with the lipid accumulation product (LAP) index and the body mass index (BMI). After analyzing the serum Mg concentration, positive correlations were observed with E2, PINP, and PTH in patients with MetS. In patients without MetS, the Mg concentration in bone positively correlated with the BMI and the LAP index. Our study findings suggest that increased Mg levels could have an impact on bone tissue metabolism. Elevated serum Mg levels may be associated with changes in sex hormone concentrations and alterations in bone turnover markers. Full article
(This article belongs to the Special Issue The Role of Mg Homeostasis in Disease)
13 pages, 2427 KiB  
Article
Low Magnesium Concentration Enforces Bone Calcium Deposition Irrespective of 1,25-Dihydroxyvitamin D3 Concentration
by Usman Rashid, Sandra K. Becker, Gerhard Sponder, Susanne Trappe, Mansur A. Sandhu and Jörg R. Aschenbach
Int. J. Mol. Sci. 2023, 24(10), 8679; https://doi.org/10.3390/ijms24108679 - 12 May 2023
Cited by 1 | Viewed by 1159
Abstract
Efficient coordination between Mg2+ and vitamin D maintains adequate Ca2+ levels during lactation. This study explored the possible interaction between Mg2+ (0.3, 0.8, and 3 mM) and 1,25-dihydroxyvitamin D3 (1,25D; 0.05 and 5 nM) during osteogenesis using bovine mesenchymal [...] Read more.
Efficient coordination between Mg2+ and vitamin D maintains adequate Ca2+ levels during lactation. This study explored the possible interaction between Mg2+ (0.3, 0.8, and 3 mM) and 1,25-dihydroxyvitamin D3 (1,25D; 0.05 and 5 nM) during osteogenesis using bovine mesenchymal stem cells. After 21 days, differentiated osteocytes were subjected to OsteoImage analysis, alkaline phosphatase (ALP) activity measurements, and immunocytochemistry of NT5E, ENG (endoglin), SP7 (osterix), SPP1 (osteopontin), and the BGLAP gene product osteocalcin. The mRNA expression of NT5E, THY1, ENG, SP7, BGLAP, CYP24A1, VDR, SLC41A1, SLC41A2, SLC41A3, TRPM6, TRPM7, and NIPA1 was also assessed. Reducing the Mg2+ concentration in the medium increased the accumulation of mineral hydroxyapatite and ALP activity. There was no change in the immunocytochemical localization of stem cell markers. Expression of CYP24A1 was higher in all groups receiving 5 nM 1,25D. There were tendencies for higher mRNA abundance of THY1, BGLAP, and NIPA1 in cells receiving 0.3 mM Mg2+ and 5 nM 1,25D. In conclusion, low levels of Mg2+ greatly enhanced the deposition of bone hydroxyapatite matrix. The effect of Mg2+ was not modulated by 1,25D, although the expression of certain genes (including BGLAP) tended to be increased by the combination of low Mg2+ and high 1,25D concentrations. Full article
(This article belongs to the Special Issue The Role of Mg Homeostasis in Disease)
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13 pages, 3788 KiB  
Article
The Role of Txnip in Mediating Low-Magnesium-Driven Endothelial Dysfunction
by Laura Locatelli, Giorgia Fedele and Jeanette A. Maier
Int. J. Mol. Sci. 2023, 24(9), 8351; https://doi.org/10.3390/ijms24098351 - 06 May 2023
Cited by 1 | Viewed by 1197
Abstract
Magnesium deficiency is associated with a greater risk of developing cardiovascular diseases since this cation is fundamental in regulating vascular function. This clinical evidence is sustained by in vitro studies showing that culturing endothelial cells in low concentrations of magnesium promotes the acquisition [...] Read more.
Magnesium deficiency is associated with a greater risk of developing cardiovascular diseases since this cation is fundamental in regulating vascular function. This clinical evidence is sustained by in vitro studies showing that culturing endothelial cells in low concentrations of magnesium promotes the acquisition of a pro-oxidant and pro-inflammatory phenotype. Here, we show that the increase in reactive oxygen species in endothelial cells in low-magnesium-containing medium is due to the upregulation of the pro-oxidant protein thioredoxin interacting protein (TXNIP), with a consequent accumulation of lipid droplets and increase in endothelial permeability through the downregulation and relocalization of junctional proteins. Silencing TXNIP restores the endothelial barrier and lipid content. Because (i) mitochondria serve multiple roles in shaping cell function, health and survival and (ii) mitochondria are the main intracellular stores of magnesium, it is of note that no significant alterations were detected in their morphology and dynamics in our experimental model. We conclude that TXNIP upregulation contributes to low-magnesium-induced endothelial dysfunction in vitro. Full article
(This article belongs to the Special Issue The Role of Mg Homeostasis in Disease)
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21 pages, 8391 KiB  
Article
The Interactions of Magnesium Sulfate and Cromoglycate in a Rat Model of Orofacial Pain; The Role of Magnesium on Mast Cell Degranulation in Neuroinflammation
by Dragana Srebro, Branko Dožić, Sonja Vučković, Katarina Savić Vujović, Branislava Medić Brkić, Ivan Dožić and Milorad Srebro
Int. J. Mol. Sci. 2023, 24(7), 6241; https://doi.org/10.3390/ijms24076241 - 26 Mar 2023
Viewed by 2450
Abstract
Mast cell degranulation impacts the development of pain and inflammation during tissue injury. We investigated the antinociceptive effect of a combination of cromoglycate and magnesium in the orofacial model of pain and the histological profile of the effect of magnesium in orofacial pain. [...] Read more.
Mast cell degranulation impacts the development of pain and inflammation during tissue injury. We investigated the antinociceptive effect of a combination of cromoglycate and magnesium in the orofacial model of pain and the histological profile of the effect of magnesium in orofacial pain. In male Wistar rats, formalin (1.5%, 100 µL) was injected subcutaneously into the right upper lip of rats after cromoglycate and/or magnesium. Pain was measured as the total time spent on pain-related behavior. Toluidine blue staining was used to visualize mast cells under the light microscope. In the formalin test, in phase 1, magnesium antagonized the antinociceptive effect of cromoglycate, while in phase 2, it potentiated or inhibited its effect. Magnesium significantly reduced mast cell degranulation in the acute phase by about 23% and in the second phase by about 40%. Pearson’s coefficient did not show a significant correlation between mast cell degranulation and pain under treatment with magnesium. The cromoglycate–magnesium sulfate combination may prevent the development of inflammatory orofacial pain. The effect of a combination of cromoglycate–magnesium sulfate depends on the nature of the pain and the individual effects of the drugs. Magnesium reduced orofacial inflammation in the periphery, and this effect did not significantly contribute to its analgesic effect. Full article
(This article belongs to the Special Issue The Role of Mg Homeostasis in Disease)
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Review

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19 pages, 2213 KiB  
Review
Magnesium and Vascular Calcification in Chronic Kidney Disease: Current Insights
by Shari J. Zaslow, Gustavo H. Oliveira-Paula and Wei Chen
Int. J. Mol. Sci. 2024, 25(2), 1155; https://doi.org/10.3390/ijms25021155 - 18 Jan 2024
Viewed by 1031
Abstract
Magnesium (Mg) plays crucial roles in multiple essential biological processes. As the kidneys are the primary organ responsible for maintaining the blood concentration of Mg, people with chronic kidney disease (CKD) may develop disturbances in Mg. While both hyper- and hypomagnesemia may lead [...] Read more.
Magnesium (Mg) plays crucial roles in multiple essential biological processes. As the kidneys are the primary organ responsible for maintaining the blood concentration of Mg, people with chronic kidney disease (CKD) may develop disturbances in Mg. While both hyper- and hypomagnesemia may lead to adverse effects, the consequences associated with hypomagnesemia are often more severe and lasting. Importantly, observational studies have shown that CKD patients with hypomagnesemia have greater vascular calcification. Vascular calcification is accelerated and contributes to a high mortality rate in the CKD population. Both in vitro and animal studies have demonstrated that Mg protects against vascular calcification via several potential mechanisms, such as inhibiting the formation of both hydroxyapatite and pathogenic calciprotein particles as well as limiting osteogenic differentiation, a process in which vascular smooth muscle cells in the media layer of the arteries transform into bone-like cells. These preclinical findings have led to several important clinical trials that have investigated the effects of Mg supplementation on vascular calcification in people with CKD. Interestingly, two major clinical studies produced contradictory findings, resulting in a state of equipoise. This narrative review provides an overview of our current knowledge in the renal handling of Mg in health and CKD and the underlying mechanisms by which Mg may protect against vascular calcification. Lastly, we evaluate the strength of evidence from clinical studies on the efficacy of Mg supplementation and discuss future research directions. Full article
(This article belongs to the Special Issue The Role of Mg Homeostasis in Disease)
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