38 results on '"Castiglioni, Sara"'
Search Results
2. Low extracellular magnesium induces phenotypic and metabolic alterations in C2C12-derived myotubes.
- Author
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Zocchi M, Bartolini M, Maier JA, and Castiglioni S
- Subjects
- Muscle, Skeletal metabolism, Myosin Heavy Chains metabolism, Magnesium metabolism, Muscle Fibers, Skeletal metabolism
- Abstract
Magnesium (Mg) has a pivotal role in upholding skeletal muscle health and optimizing performance. Its deficiency decreases muscle strength, and an association has been reported between Mg intake and sarcopenia. To gain a comprehensive understanding of the repercussions arising from low Mg concentrations on muscle behavior, we employed an in vitro model utilizing C2C12-derived myotubes. Myotubes cultured in low Mg show a significant reduction of thickness and a concomitant down-regulation of myosin heavy chain (MyHC), Myog and Myomixer. In parallel, myotubes shape their metabolism. Glycolysis is inhibited and beta-oxidation increases. These metabolic changes are consistent with the increase of MyHC I (slow) vs. MyHC II (fast) expression. We identified an essential player in these changes, namely nitric oxide (NO), as the increase in NO production appeared to orchestrate the observed modifications in myotube behavior and metabolism under low Mg conditions. Understanding these underlying mechanisms may pave the way for targeted interventions to ameliorate muscle-related conditions associated with Mg deficiency and contribute to enhancing overall muscle health and function., (© 2023. The Author(s).)
- Published
- 2023
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3. Magnesium Homeostasis in Myogenic Differentiation-A Focus on the Regulation of TRPM7, MagT1 and SLC41A1 Transporters.
- Author
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Zocchi M, Locatelli L, Zuccotti GV, Mazur A, Béchet D, Maier JA, and Castiglioni S
- Subjects
- Animals, Cation Transport Proteins genetics, Cell Line, Mice, TRPM Cation Channels genetics, Cation Transport Proteins metabolism, Cell Differentiation, Magnesium metabolism, Muscle Development, Myoblasts metabolism, TRPM Cation Channels metabolism
- Abstract
Magnesium (Mg) is essential for skeletal muscle health, but little is known about the modulation of Mg and its transporters in myogenic differentiation. Here, we show in C2C12 murine myoblasts that Mg concentration fluctuates during their differentiation to myotubes, declining early in the process and reverting to basal levels once the cells are differentiated. The level of the Mg transporter MagT1 decreases at early time points and is restored at the end of the process, suggesting a possible role in the regulation of intracellular Mg concentration. In contrast, TRPM7 is rapidly downregulated and remains undetectable in myotubes. The reduced amounts of TRPM7 and MagT1 are due to autophagy, one of the proteolytic systems activated during myogenesis and essential for the membrane fusion process. Moreover, we investigated the levels of SLC41A1, which increase once cells are differentiated, mainly through transcriptional regulation. In conclusion, myogenesis is associated with alterations of Mg homeostasis finely tuned through the modulation of MagT1, TRPM7 and SLC41A1.
- Published
- 2022
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4. Editorial of Special Issue "Magnesium in Human Health and Disease".
- Author
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Castiglioni S
- Subjects
- Humans, Magnesium Deficiency metabolism, Health, Magnesium metabolism
- Abstract
The fundamental role of magnesium in human health is extensively discussed in the review by Fiorentini and colleagues [...].
- Published
- 2021
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5. Magnesium and inflammation: Advances and perspectives.
- Author
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Maier JA, Castiglioni S, Locatelli L, Zocchi M, and Mazur A
- Subjects
- Animals, Cation Transport Proteins metabolism, Homeostasis physiology, Humans, Endothelial Cells metabolism, Inflammation metabolism, Magnesium metabolism, Magnesium Deficiency metabolism
- Abstract
Magnesium is an essential element of life, involved in the regulation of metabolism and homeostasis of all the tissues. It also regulates immunological functions, acting on the cells of innate and adaptive immune systems. Magnesium deficiency primes phagocytes, enhances granulocyte oxidative burst, activates endothelial cells and increases the levels of cytokines, thus promoting inflammation. Consequently, a low magnesium status, which is often underdiagnosed, potentiates the reactivity to various immune challenges and is implicated in the pathophysiology of many common chronic diseases. Here we summarize recent advances supporting the link between magnesium deficiency, inflammatory responses and diseases, and offer new hints towards a better understanding of the underlying mechanisms., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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6. Magnesium Deficiency Alters Expression of Genes Critical for Muscle Magnesium Homeostasis and Physiology in Mice.
- Author
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Bayle D, Coudy-Gandilhon C, Gueugneau M, Castiglioni S, Zocchi M, Maj-Zurawska M, Palinska-Saadi A, Mazur A, Béchet D, and Maier JA
- Subjects
- Animals, Disease Models, Animal, Energy Metabolism genetics, Mice, Mice, Inbred C57BL, Muscle Fibers, Skeletal metabolism, Signal Transduction genetics, Cation Transport Proteins metabolism, Homeostasis genetics, Magnesium metabolism, Magnesium Deficiency genetics, Muscle, Skeletal metabolism
- Abstract
Chronic Mg
2+ deficiency is the underlying cause of a broad range of health dysfunctions. As 25% of body Mg2+ is located in the skeletal muscle, Mg2+ transport and homeostasis systems (MgTHs) in the muscle are critical for whole-body Mg2+ homeostasis. In the present study, we assessed whether Mg2+ deficiency alters muscle fiber characteristics and major pathways regulating muscle physiology. C57BL/6J mice received either a control, mildly, or severely Mg2+ -deficient diet (0.1%; 0.01%; and 0.003% Mg2+ wt/wt, respectively) for 14 days. Mg2+ deficiency slightly decreased body weight gain and muscle Mg2+ concentrations but was not associated with detectable variations in gastrocnemius muscle weight, fiber morphometry, and capillarization. Nonetheless, muscles exhibited decreased expression of several MgTHs ( MagT1 , CNNM2 , CNNM4 , and TRPM6 ). Moreover, TaqMan low-density array (TLDA) analyses further revealed that, before the emergence of major muscle dysfunctions, even a mild Mg2+ deficiency was sufficient to alter the expression of genes critical for muscle physiology, including energy metabolism, muscle regeneration, proteostasis, mitochondrial dynamics, and excitation-contraction coupling.- Published
- 2021
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7. A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying Mechanisms.
- Author
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Locatelli L, Cazzaniga A, Fedele G, Zocchi M, Scrimieri R, Moscheni C, Castiglioni S, and Maier JA
- Subjects
- Antibiotics, Antineoplastic pharmacology, Cell Line, Tumor, Colonic Neoplasms metabolism, Colonic Neoplasms pathology, Drug Resistance, Neoplasm, HL-60 Cells, Humans, Leukemia, Promyelocytic, Acute metabolism, Leukemia, Promyelocytic, Acute pathology, Protein Serine-Threonine Kinases metabolism, TRPM Cation Channels metabolism, Colonic Neoplasms drug therapy, Doxorubicin pharmacology, Leukemia, Promyelocytic, Acute drug therapy, Magnesium metabolism, Reactive Oxygen Species metabolism
- Abstract
Chemoresistance causes cancer relapse and metastasis, thus remaining the major obstacle to cancer therapy. While some light has been shed on the underlying mechanisms, it is clear that chemoresistance is a multifaceted problem strictly interconnected with the high heterogeneity of neoplastic cells. We utilized two different human cell lines, i.e., LoVo colon cancer and promyelocytic leukemia HL60 cells sensitive and resistant to doxorubicin (DXR), largely used as a chemotherapeutic and frequently leading to chemoresistance. LoVo and HL60 resistant cells accumulate less reactive oxygen species by differently modulating the levels of some pro- and antioxidant proteins. Moreover, the content of intracellular magnesium, known to contribute to protect cells from oxidative stress, is increased in DXR-resistant LoVo through the upregulation of MagT1 and in DXR-resistant HL60 because of the overexpression of TRPM7. In addition, while no major differences in mitochondrial mass are observed in resistant HL60 and LoVo cells, fragmented mitochondria due to increased fission and decreased fusion are detected only in resistant LoVo cells. We conclude that DXR-resistant cells evolve adaptive mechanisms to survive DXR cytotoxicity by activating different molecular pathways.
- Published
- 2021
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8. [The magnesium global network (MaGNet) to promote research on magnesium in diseases focusing on covid-19].
- Author
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Wolf FI, Maier JA, Rosanoff A, Barbagallo M, Baniasadi S, Castiglioni S, Cheng FC, Day SC, Costello RB, Dominguez LJ, Elin RJ, Gamboa-Gomez C, Guerrero-Romero F, Kahe K, Kisters K, Kolisek M, Kraus A, Iotti S, Mazur A, Mercado-Atri M, Merolle L, Micke O, Gletsu-Miller N, Nielsen F, O-Uchi J, Piazza O, Plesset M, Pourdowlat G, Rios FJ, Rodriguez-Moran M, Scarpati G, Shechter M, Song Y, Spence LA, Touyz RM, Trapani V, Veronese N, von Ehrlich B, Vormann J, Wallace TC, Cmer Center For Magnesium Education Research, Gesellschaft Für Magnesium-Forschung E V Germany, and Sdrm Society International Society For The Development Of Research On Magnesium
- Subjects
- Aging, COVID-19 prevention & control, Cardiovascular Diseases epidemiology, Comorbidity, Congresses as Topic, Disease Susceptibility, Humans, Immune System physiology, Inflammation epidemiology, Magnesium Deficiency therapy, Metabolic Diseases epidemiology, Neoplasms epidemiology, Obesity epidemiology, Research, Societies, Scientific, COVID-19 epidemiology, Magnesium physiology, Magnesium Deficiency epidemiology
- Published
- 2021
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9. Magnesium Influences Membrane Fusion during Myogenesis by Modulating Oxidative Stress in C2C12 Myoblasts.
- Author
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Zocchi M, Béchet D, Mazur A, Maier JA, and Castiglioni S
- Subjects
- Animals, Cell Differentiation physiology, Cell Line, Mice, Magnesium metabolism, Membrane Fusion physiology, Muscle Development physiology, Myoblasts physiology, Oxidative Stress physiology
- Abstract
Magnesium (Mg) is essential to skeletal muscle where it plays a key role in myofiber relaxation. Although the importance of Mg in the mature skeletal muscle is well established, little is known about the role of Mg in myogenesis. We studied the effects of low and high extracellular Mg in C2C12 myogenic differentiation. Non-physiological Mg concentrations induce oxidative stress in myoblasts. The increase of reactive oxygen species, which occurs during the early phase of the differentiation process, inhibits myoblast membrane fusion, thus impairing myogenesis. Therefore, correct Mg homeostasis, also maintained through a correct dietary intake, is essential to assure the regenerative capacity of skeletal muscle fibers.
- Published
- 2021
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10. Magnesium Is a Key Regulator of the Balance between Osteoclast and Osteoblast Differentiation in the Presence of Vitamin D₃.
- Author
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Mammoli F, Castiglioni S, Parenti S, Cappadone C, Farruggia G, Iotti S, Davalli P, Maier JAM, Grande A, and Frassineti C
- Subjects
- Cell Line, Tumor, Cell Proliferation drug effects, Cholecalciferol pharmacology, Gene Expression Profiling, Humans, Macrophages cytology, Macrophages drug effects, Macrophages metabolism, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells drug effects, Mesenchymal Stem Cells metabolism, Monocytes cytology, Monocytes drug effects, Monocytes metabolism, Osteoblasts drug effects, Osteoclasts drug effects, U937 Cells, Cell Differentiation, Cholecalciferol metabolism, Magnesium metabolism, Osteoblasts cytology, Osteoblasts metabolism, Osteoclasts cytology, Osteoclasts metabolism
- Abstract
Magnesium (Mg) is crucial for bone health. Low concentrations of Mg inhibit the activity of osteoblasts while promoting that of osteoclasts, with the final result of inducing osteopenia. Conversely, little is known about the effects of high concentrations of extracellular Mg on osteoclasts and osteoblasts. Since the differentiation and activation of these cells is coordinated by vitamin D₃ (VD3), we investigated the effects of high extracellular Mg, as well as its impact on VD3 activity, in these cells. U937 cells were induced to osteoclastic differentiation by VD3 in the presence of supra-physiological concentrations (>1 mM) of extracellular Mg. The effect of high Mg concentrations was also studied in human bone-marrow-derived mesenchymal stem cells (bMSCs) induced to differentiate into osteoblasts by VD3. We demonstrate that high extra-cellular Mg levels potentiate VD3-induced osteoclastic differentiation, while decreasing osteoblastogenesis. We hypothesize that Mg might reprogram VD3 activity on bone remodeling, causing an unbalanced activation of osteoclasts and osteoblasts.
- Published
- 2019
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11. Magnesium Deprivation Potentiates Human Mesenchymal Stem Cell Transcriptional Remodeling.
- Author
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Sargenti A, Castiglioni S, Olivi E, Bianchi F, Cazzaniga A, Farruggia G, Cappadone C, Merolle L, Malucelli E, Ventura C, Maier JAM, and Iotti S
- Subjects
- Adipose Tissue cytology, Adult, Bone Marrow Cells cytology, Cell Cycle genetics, Cell Differentiation genetics, Female, Gene Expression Regulation, Humans, Osteogenesis genetics, Reactive Oxygen Species metabolism, Magnesium metabolism, Mesenchymal Stem Cells metabolism, Transcription, Genetic
- Abstract
Magnesium plays a pivotal role in energy metabolism and in the control of cell growth. While magnesium deprivation clearly shapes the behavior of normal and neoplastic cells, little is known on the role of this element in cell differentiation. Here we show that magnesium deficiency increases the transcription of multipotency markers and tissue-specific transcription factors in human adipose-derived mesenchymal stem cells exposed to a mixture of natural molecules, i.e., hyaluronic, butyric and retinoid acids, which tunes differentiation. We also demonstrate that magnesium deficiency accelerates the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. We argue that magnesium deprivation generates a stressful condition that modulates stem cell plasticity and differentiation potential. These studies indicate that it is possible to remodel transcription in mesenchymal stem cells by lowering extracellular magnesium without the need for genetic manipulation, thus offering new hints for regenerative medicine applications.
- Published
- 2018
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12. Single cell versus large population analysis: cell variability in elemental intracellular concentration and distribution.
- Author
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Malucelli E, Procopio A, Fratini M, Gianoncelli A, Notargiacomo A, Merolle L, Sargenti A, Castiglioni S, Cappadone C, Farruggia G, Lombardo M, Lagomarsino S, Maier JA, and Iotti S
- Subjects
- Cell Count, Cell Line, Tumor, Human Umbilical Vein Endothelial Cells, Humans, Synchrotrons, X-Rays, Fluorescent Dyes chemistry, Magnesium analysis, Microscopy, Fluorescence methods, Optical Imaging methods, Single-Cell Analysis methods
- Abstract
The quantification of elemental concentration in cells is usually performed by analytical assays on large populations missing peculiar but important rare cells. The present article aims at comparing the elemental quantification in single cells and cell population in three different cell types using a new approach for single cells elemental analysis performed at sub-micrometer scale combining X-ray fluorescence microscopy and atomic force microscopy. The attention is focused on the light element Mg, exploiting the opportunity to compare the single cell quantification to the cell population analysis carried out by a highly Mg-selective fluorescent chemosensor. The results show that the single cell analysis reveals the same Mg differences found in large population of the different cell strains studied. However, in one of the cell strains, single cell analysis reveals two cells with an exceptionally high intracellular Mg content compared with the other cells of the same strain. The single cell analysis allows mapping Mg and other light elements in whole cells at sub-micrometer scale. A detailed intensity correlation analysis on the two cells with the highest Mg content reveals that Mg subcellular localization correlates with oxygen in a different fashion with respect the other sister cells of the same strain. Graphical abstract Single cells or large population analysis this is the question!
- Published
- 2018
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13. Serum magnesium and calcium levels in infertile women during a cycle of reproductive assistance.
- Author
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Grossi E, Castiglioni S, Moscheni C, Antonazzo P, Cetin I, and Savasi VM
- Subjects
- Adult, Female, Humans, Middle Aged, Ovulation Induction, Reference Values, Young Adult, Calcium blood, Infertility, Female blood, Magnesium blood, Reproductive Techniques, Assisted
- Abstract
Magnesium (Mg) and calcium (Ca) are essential cations for women's preconception health. It is well known that, in blood, the concentration of ionized form of these two cations is temporally altered during menstrual cycle, suggesting a correlation between sex steroid hormones and serum calcium and magnesium levels. Evidence from literature suggests that in assisted reproductive technology increasing estrogens during ovarian hyperstimulation may also modulate serum magnesium and calcium levels. Therefore, we first examined total serum magnesium and calcium levels during follicular phase in a large population of infertile patients who underwent intrauterine insemination (IUI). The results were compared to a group of fertile women. Successively, we studied the total serum magnesium and calcium concentrations in infertile patients before and after ovarian hyperstimulation for in vitro fertilization (IVF). Results highlight that total serum concentration of magnesium and calcium does not seem altered in infertile women. During stimulation with gonadotropins, the values of the two cations do not change significantly in ovarian-stimulated women. However, we found a downward trend in the total magnesium and calcium levels in relation to the rising estrogens.
- Published
- 2017
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14. Extracellular magnesium and calcium blockers modulate macrophage activity.
- Author
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Libako P, Nowacki W, Castiglioni S, Mazur A, and Maier JA
- Subjects
- Animals, Calcium Channel Blockers metabolism, Cells, Cultured, Dose-Response Relationship, Drug, Macrophages metabolism, Magnesium metabolism, Mice, Mice, Inbred BALB C, Structure-Activity Relationship, Verapamil metabolism, Calcium Channel Blockers pharmacology, Macrophages drug effects, Magnesium pharmacology, Verapamil pharmacology
- Abstract
Magnesium (Mg) possesses anti-inflammatory properties, partly because it antagonizes calcium (Ca) and inhibits L-type Ca channels. Our aim was to determine the effects of different concentrations of extracellular Mg, with or without Ca-channel blockers, in macrophages. A macrophage-like cell line J774.E was cultured in different concentrations of extracellular Mg and exposed to i) the phorbol ester PMA to induce the production of reactive oxygen species ii) lipopolysaccharide to induce the production of pro-inflammatory cytokines, or iii) ovalbumin to study endocytosis. The Ca antagonists verapamil and/or TMB-8 were used to interfere with Ca homeostasis. Different concentrations of extracellular Mg did not impact on endocytosis, while Ca antagonists markedly decreased it. Low extracellular Mg exacerbated, whereas Ca antagonists inhibited, PMA-induced production of free radicals. Ca blockers prevented lipopolysaccharide-induced transcription and release of IL-1β, IL-6 and TNF-α, while extracellular Mg had only a marginal effect. Ca channel inhibitors markedly reduced the activity of J774.E cells, thus underscoring the critical role of Ca in the non-specific immune response, a role which was, in some instances, also modulated by extracellular Mg.
- Published
- 2016
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15. Magnesium homeostasis in colon carcinoma LoVo cells sensitive or resistant to doxorubicin.
- Author
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Castiglioni S, Cazzaniga A, Trapani V, Cappadone C, Farruggia G, Merolle L, Wolf FI, Iotti S, and Maier JAM
- Subjects
- Antibiotics, Antineoplastic pharmacology, Blotting, Western, Calpain antagonists & inhibitors, Calpain metabolism, Cell Line, Tumor, Colonic Neoplasms genetics, Colonic Neoplasms metabolism, Colonic Neoplasms pathology, Cysteine Proteinase Inhibitors pharmacology, Dipeptides pharmacology, Drug Resistance, Neoplasm genetics, Homeostasis genetics, Humans, Ion Transport drug effects, Ion Transport genetics, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, TRPM Cation Channels genetics, TRPM Cation Channels metabolism, Doxorubicin pharmacology, Gene Expression Regulation, Neoplastic drug effects, Homeostasis drug effects, Magnesium metabolism
- Abstract
Neoplastic cells accumulate magnesium, an event which provides selective advantages and is frequently associated with TRPM7 overexpression. Little is known about magnesium homeostasis in drug-resistant cancer cells. Therefore, we used the colon cancer LoVo cell model and compared doxorubicin-resistant to sensitive cells. In resistant cells the concentration of total magnesium is higher while its influx capacity is lower than in sensitive cells. Accordingly, resistant cells express lower amounts of the TRPM6 and 7, both involved in magnesium transport. While decreased TRPM6 levels are due to transcriptional regulation, post-transcriptional events are involved in reducing the amounts of TRPM7. Indeed, the calpain inhibitor calpeptin markedly increases the levels of TRPM7 in resistant cells. In doxorubicin-sensitive cells, silencing TRPM7 shifts the phenotype to one more similar to resistant cells, since in these cells silencing TRPM7 significantly decreases the influx of magnesium, increases its intracellular concentration and increases resistance to doxorubicin. On the other hand, calpain inhibition upregulates TRPM7, decreases intracellular magnesium and enhances the sensitivity to doxorubicin of resistant LoVo cells. We conclude that in LoVo cells drug resistance is associated with alteration of magnesium homeostasis through modulation of TRPM7. Our data suggest that TRPM7 expression may be an additional undisclosed player in chemoresistance.
- Published
- 2015
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16. Extracellular Mg concentration and Ca blockers modulate the initial steps of the response of Th2 lymphocytes in co-culture with macrophages and dendritic cells.
- Author
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Libako P, Miller J, Nowacki W, Castiglioni S, Maier JA, and Mazur A
- Subjects
- Bone Marrow Cells cytology, Bone Marrow Cells drug effects, Bone Marrow Cells immunology, Cations, Divalent, Coculture Techniques, Dendritic Cells cytology, Dendritic Cells immunology, Endocytosis drug effects, Gallic Acid analogs & derivatives, Gallic Acid pharmacology, Humans, Interleukin-10 biosynthesis, Interleukin-10 metabolism, Interleukin-4 biosynthesis, Interleukin-4 metabolism, Macrophages cytology, Macrophages immunology, Th2 Cells cytology, Th2 Cells immunology, Verapamil pharmacology, Calcium pharmacology, Calcium Channel Blockers pharmacology, Dendritic Cells drug effects, Macrophages drug effects, Magnesium pharmacology, Th2 Cells drug effects
- Abstract
Magnesium is highly involved in the metabolic network such that even subtle disturbances in its homeostasis affect many cellular functions, including calcium homeostasis, signal transduction, energy metabolism, membrane stability and cell proliferation. Recently, magnesium level has been proposed to modulate the priming and activity of immune cells. We studied the behavior of antigen-presenting cells (APCs) and T lymphocytes after altering the magnesium/calcium balance. We used two different populations of primary APCs, i.e. bone marrow-derived dendritic cells and bone marrow-derived macrophages, while D10.G4.1 cells served as a model of responding Th2 cells. Our principal findings are the following: (i) the extracellular magnesium concentration had no significant impact on endocytosis by bone marrow-derived APCs, (ii) high concentrations of extracellular magnesium, with or without calcium antagonists, significantly decreased IL-4 and IL-10 secretion by Th2 cells in a co-culture system of APCs and Th2 lymphocytes, (iii) proliferation of Th2 cells in co-culture systems was significantly inhibited by calcium antagonists independently from extracellular magnesium concentrations. Our results suggest that alterations of magnesium and calcium homeostasis impact on some crucial steps of the immune response.
- Published
- 2015
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17. Potential interplay between NFκB and PPARγ in human dermal microvascular endothelial cells cultured in low magnesium.
- Author
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Castiglioni S, Cazzaniga A, and Maier JA
- Subjects
- Cells, Cultured, Dermis cytology, Dermis drug effects, Endothelial Cells drug effects, Humans, Microcirculation drug effects, Dermis metabolism, Endothelial Cells metabolism, Magnesium administration & dosage, Microcirculation physiology, NF-kappa B metabolism, PPAR gamma metabolism
- Abstract
Dermal microvascular endothelial cells contribute to cutaneous inflammation by secreting proinflammatory cytokines and chemokines. We show here that low extracellular magnesium stimulates the secretion of interleukin 8 and monocyte chemoattractant protein-1 in dermal microvascular endothelial cells. This secretory pattern might result from interplay between NFκB, the master regulator of inflammation, and PPARγ, a transcription factor that has emerged as an inhibitor of inflammation. Indeed, both NFκB and PPARγ are activated in dermal microvascular endothelial cells cultured in low magnesium-containing medium. In conclusion, we hypothesize that PPARγ and NFκB might contribute to the response of these cells to low Mg.
- Published
- 2014
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18. Magnesium and osteoporosis: current state of knowledge and future research directions.
- Author
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Castiglioni S, Cazzaniga A, Albisetti W, and Maier JA
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- Animals, Bone and Bones drug effects, Bone and Bones metabolism, Disease Models, Animal, Homeostasis, Humans, Magnesium Deficiency complications, Magnesium Deficiency drug therapy, Osteoporosis complications, Parathyroid Hormone metabolism, Dietary Supplements, Magnesium administration & dosage, Osteoporosis drug therapy, Osteoporosis prevention & control
- Abstract
A tight control of magnesium homeostasis seems to be crucial for bone health. On the basis of experimental and epidemiological studies, both low and high magnesium have harmful effects on the bones. Magnesium deficiency contributes to osteoporosis directly by acting on crystal formation and on bone cells and indirectly by impacting on the secretion and the activity of parathyroid hormone and by promoting low grade inflammation. Less is known about the mechanisms responsible for the mineralization defects observed when magnesium is elevated. Overall, controlling and maintaining magnesium homeostasis represents a helpful intervention to maintain bone integrity.
- Published
- 2013
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19. Extracellular magnesium and in vitro cell differentiation: different behaviour of different cells.
- Author
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Castiglioni S, Leidi M, Carpanese E, and Maier JA
- Subjects
- 3T3-L1 Cells, Animals, Collagen pharmacology, Drug Combinations, Human Umbilical Vein Endothelial Cells drug effects, Humans, Laminin pharmacology, Mice, Proteoglycans pharmacology, U937 Cells, Adipocytes cytology, Cell Differentiation drug effects, Extracellular Space metabolism, Human Umbilical Vein Endothelial Cells cytology, Magnesium pharmacology
- Abstract
The contribution of magnesium to cell differentiation is not clear. Some studies indicate that low extracellular magnesium promotes cell differentiation, while others reach opposite conclusions. We evaluated the effects of different concentrations of extracellular magnesium on the differentiation of three in vitro experimental models: human endothelial cells seeded onto Matrigel; phorbol ester-treated myeloid leukemia U937 cells; and 3T3-L1 pre-adipocytes exposed to a hormonal cocktail containing dexamethasone and insulin. The differentiation of endothelial cells and pre-adipocytes seems to be independent of extracellular Mg concentration. Conversely, magnesium deficiency retards, while high extracellular magnesium accelerates phorbol ester-induced U937 cell differentiation, probably by interfering with calcium homeostasis or with the activity of kinases. We conclude that the extracellular magnesium concentration affects the differentiation of various cell types.
- Published
- 2013
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20. Blocking the rise of intracellular calcium inhibits the growth of cells cultured in different concentrations of magnesium.
- Author
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Libako P, Castiglioni S, Baldoli E, Mazur A, Nowacki W, and Maier JA
- Subjects
- Animals, Biological Transport drug effects, Cell Line, Cell Proliferation drug effects, Gallic Acid analogs & derivatives, Gallic Acid pharmacology, Mice, Verapamil pharmacology, Calcium metabolism, Magnesium pharmacology
- Abstract
Divalent cations, especially calcium and magnesium, have been shown to play an important regulatory role in endothelial and immune cells. To learn more about the interaction of these two metals in the regulation of cell growth, we altered the calcium/magnesium ratio by culturing human endothelial cells, macrophages, and T lymphocytes in media containing different concentrations of magnesium. We observed that the growth of the three cell types was retarded in low extracellular magnesium, and this retardation is particularly evident in highly proliferating cells. High concentrations of magnesium does not exert any effect on cell growth. When (i) calcium influx was blocked by adding the calcium antagonist verapamil, and (ii) calcium release from intracellular stores was inhibited by exposure to TMB-8, the growth of endothelial cells, macrophages, and T lymphocytes was inhibited. In particular, the release of calcium from intracellular stores seems to be more important than its influx in sustaining cell proliferation. Our results indicate that calcium plays a crucial role in mediating cell proliferation independently from the extracellular concentrations of magnesium.
- Published
- 2012
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21. Magnesium and cancer: a dangerous liason.
- Author
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Castiglioni S and Maier JA
- Subjects
- Animals, Cell Transformation, Neoplastic metabolism, Cell Transformation, Neoplastic pathology, Cells, Cultured, Disease Models, Animal, Humans, Magnesium Deficiency complications, Neoplasms etiology, Magnesium metabolism, Magnesium Deficiency metabolism, Neoplasms metabolism, Neoplasms pathology
- Abstract
A complex relationship links magnesium and cancer. The aim of this review is to revisit current knowledge concerning the contribution of magnesium to tumorigenesis, from transformed cells to animal models, and ending with data from human studies. Cultured neoplastic cells tend to accumulate magnesium. High intracellular levels of the cation seem to confer a metabolic advantage to the cells, contribute to alterations of the genome, and promote the acquisition of an immortal phenotype. In magnesium-deficient mice, low magnesium both limits and fosters tumorigenesis, since inhibition of tumor growth at its primary site is observed in the face of increased metastatic colonization. Epidemiological studies identify magnesium deficiency as a risk factor for some types of human cancers. In addition, impaired magnesium homeostasis is reported in cancer patients, and frequently complicates therapy with some anti-cancer drugs. More studies should be undertaken in order to disclose whether a simple and inexpensive intervention to optimize magnesium intake might be helpful in the prevention and treatment of cancer.
- Published
- 2011
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22. Impact of Inducible Nitric Oxide Synthase Activation on Endothelial Behavior under Magnesium Deficiency.
- Author
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Fedele, Giorgia, Castiglioni, Sara, Trapani, Valentina, Zafferri, Isabella, Bartolini, Marco, Casati, Silvana M., Ciuffreda, Pierangela, Wolf, Federica I., and Maier, Jeanette A.
- Abstract
Endothelial dysfunction is a crucial event in the early pathogenesis of cardiovascular diseases and is linked to magnesium (Mg) deficiency. Indeed, in endothelial cells, low Mg levels promote the acquisition of a pro-inflammatory and pro-atherogenic phenotype. This paper investigates the mechanisms by which Mg deficiency promotes oxidative stress and affects endothelial behavior in human umbilical vascular endothelial cells (HUVECs). Our data show that low Mg levels trigger oxidative stress initially by increasing NAPDH oxidase activity and then by upregulating the pro-oxidant thioredoxin-interacting protein TXNIP. The overproduction of reactive oxygen species (ROS) activates NF-κB, leading to its increased binding to the inducible nitric oxide synthase (iNOS) promoter, with the consequent increase in iNOS expression. The increased levels of nitric oxide (NO) generated by upregulated iNOS contribute to disrupting endothelial cell function by inhibiting growth and increasing permeability. In conclusion, we provide evidence that multiple mechanisms contribute to generate a pro-oxidant state under low-Mg conditions, ultimately affecting endothelial physiology. These data add support to the notion that adequate Mg levels play a significant role in preserving cardiovascular health and may suggest new approaches to prevent or manage cardiovascular diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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23. Single cell versus large population analysis: cell variability in elemental intracellular concentration and distribution
- Author
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Malucelli, Emil, Procopio, Alessandra, Fratini, Michela, Gianoncelli, Alessandra, Notargiacomo, Andrea, Merolle, Lucia, Sargenti, Azzurra, Castiglioni, Sara, Cappadone, Concettina, Farruggia, Giovanna, Lombardo, Marco, Lagomarsino, Stefano, Maier, Jeanette A., and Iotti, Stefano
- Published
- 2017
- Full Text
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24. The Effects of Sirolimus and Magnesium on Primary Human Coronary Endothelial Cells: An In Vitro Study.
- Author
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Fedele, Giorgia, Castiglioni, Sara, Maier, Jeanette A. M., and Locatelli, Laura
- Subjects
- *
RAPAMYCIN , *ENDOTHELIAL cells , *MYOCARDIAL infarction , *PERCUTANEOUS coronary intervention , *MAGNESIUM , *MAGNESIUM alloys , *MUSCLE cells - Abstract
Drug eluting magnesium (Mg) bioresorbable scaffolds represent a novel paradigm in percutaneous coronary intervention because Mg-based alloys are biocompatible, have adequate mechanical properties and can be resorbed without adverse events. Importantly, Mg is fundamental in many biological processes, mitigates the inflammatory response and is beneficial for the endothelium. Sirolimus is widely used as an antiproliferative agent in drug eluting stents to inhibit the proliferation of smooth muscle cells, thus reducing the occurrence of stent restenosis. Little is known about the potential interplay between sirolimus and Mg in cultured human coronary artery endothelial cells (hCAEC). Therefore, the cells were treated with sirolimus in the presence of different concentrations of extracellular Mg. Cell viability, migration, barrier function, adhesivity and nitric oxide synthesis were assessed. Sirolimus impairs the viability of subconfluent, but not of confluent cells independently from the concentration of Mg in the culture medium. In confluent cells, sirolimus inhibits migration, while it cooperates with Mg in exerting an anti-inflammatory action that might have a role in preventing restenosis and thrombosis. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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25. High Magnesium and Sirolimus on Rabbit Vascular Cells—An In Vitro Proof of Concept
- Author
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Fedele, Giorgia, Castiglioni, Sara, Maier, Jeanette A., and Locatelli, Laura
- Subjects
lcsh:QH201-278.5 ,lcsh:T ,rabbit coronary artery endothelial cells ,magnesium ,equipment and supplies ,lcsh:Technology ,Article ,smooth muscle cells ,sirolimus ,lcsh:TA1-2040 ,lcsh:Descriptive and experimental mechanics ,lcsh:Electrical engineering. Electronics. Nuclear engineering ,lcsh:Engineering (General). Civil engineering (General) ,lcsh:Microscopy ,lcsh:TK1-9971 ,lcsh:QC120-168.85 - Abstract
Drug-eluting bioresorbable scaffolds represent the last frontier in the field of angioplasty and stenting to treat coronary artery disease, one of the leading causes of morbidity and mortality worldwide. In particular, sirolimus-eluting magnesium-based scaffolds were recently introduced in clinical practice. Magnesium alloys are biocompatible and dissolve in body fluids, thus determining high concentrations of magnesium in the local microenvironment. Since magnesium regulates cell growth, we asked whether high levels of magnesium might interfere with the antiproliferative action of sirolimus. We performed in vitro experiments on rabbit coronary artery endothelial and smooth muscle cells (rCAEC and rSMC, respectively). The cells were treated with sirolimus in the presence of different concentrations of extracellular magnesium. Sirolimus inhibits rCAEC proliferation only in physiological concentrations of magnesium, while high concentrations prevent this effect. On the contrary, high extracellular magnesium does not rescue rSMC growth arrest by sirolimus and accentuates the inhibitory effect of the drug on cell migration. Importantly, sirolimus and magnesium do not impair rSMC response to nitric oxide. If translated into a clinical setting, these results suggest that, in the presence of sirolimus, local increases of magnesium concentration maintain normal endothelial proliferative capacity and function without affecting rSMC growth inhibition and response to vasodilators.
- Published
- 2021
26. The Presence of Blood–Brain Barrier Modulates the Response to Magnesium Salts in Human Brain Organoids.
- Author
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Cazzaniga, Alessandra, Fedele, Giorgia, Castiglioni, Sara, and Maier, Jeanette A.
- Subjects
BLOOD-brain barrier ,INDUCED pluripotent stem cells ,MAGNESIUM salts ,STEM cell culture ,ORGANOIDS ,METHYL aspartate receptors - Abstract
Magnesium (Mg) is fundamental in the brain, where it regulates metabolism and neurotransmission and protects against neuroinflammation. To obtain insights into the molecular basis of Mg action in the brain, we investigated the effects of Mg in human brain organoids, a revolutionary 3D model to study neurobiology and neuropathology. In particular, brain organoids derived from human induced pluripotent stem cells were cultured in the presence or in the absence of an in vitro-generated blood–brain barrier (BBB), and then exposed to 1 or 5 mM concentrations of inorganic and organic Mg salts (Mg sulphate (MgSO
4 ); Mg pidolate (MgPid)). We evaluated the modulation of NMDA and GABAergic receptors, and BDNF. Our data suggest that the presence of the BBB is essential for Mg to exert its effects on brain organoids, and that 5 mM of MgPid is more effective than MgSO4 in increasing the levels of GABA receptors and BDNF, and decreasing those of NMDA receptor. These results might illuminate novel pathways explaining the neuroprotective role of Mg. [ABSTRACT FROM AUTHOR]- Published
- 2022
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27. The relevance of magnesium homeostasis in COVID-19.
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Trapani, Valentina, Rosanoff, Andrea, Baniasadi, Shadi, Barbagallo, Mario, Castiglioni, Sara, Guerrero-Romero, Fernando, Iotti, Stefano, Mazur, André, Micke, Oliver, Pourdowlat, Guitti, Scarpati, Giuliana, Wolf, Federica I., and Maier, Jeanette A.
- Subjects
HOMEOSTASIS ,COVID-19 ,CHRONIC diseases ,MAGNESIUM ,AGING ,CELL proliferation ,COVID-19 pandemic ,METABOLITES - Abstract
Purpose: In less than one and a half year, the COVID-19 pandemic has nearly brought to a collapse our health care and economic systems. The scientific research community has concentrated all possible efforts to understand the pathogenesis of this complex disease, and several groups have recently emphasized recommendations for nutritional support in COVID-19 patients. In this scoping review, we aim at encouraging a deeper appreciation of magnesium in clinical nutrition, in view of the vital role of magnesium and the numerous links between the pathophysiology of SARS-CoV-2 infection and magnesium-dependent functions. Methods: By searching PubMed and Google Scholar from 1990 to date, we review existing evidence from experimental and clinical studies on the role of magnesium in chronic non-communicable diseases and infectious diseases, and we focus on recent reports of alterations of magnesium homeostasis in COVID-19 patients and their association with disease outcomes. Importantly, we conduct a census on ongoing clinical trials specifically dedicated to disclosing the role of magnesium in COVID-19. Results: Despite many methodological limitations, existing data seem to corroborate an association between deranged magnesium homeostasis and COVID-19, and call for further and better studies to explore the prophylactic or therapeutic potential of magnesium supplementation. Conclusion: We propose to reconsider the relevance of magnesium, frequently overlooked in clinical practice. Therefore, magnesemia should be monitored and, in case of imbalanced magnesium homeostasis, an appropriate nutritional regimen or supplementation might contribute to protect against SARS-CoV-2 infection, reduce severity of COVID-19 symptoms and facilitate the recovery after the acute phase. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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28. Magnesium homeostasis goes awry in chemoresistance -TRPM6, TRPM7 and MagT1 in colon carcinoma LoVo cells
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Moscheni, Claudia, Cazzaniga, Alessandra, Locatelli, Laura, Sargenti, Azzurra, Trapani, Valentina, Sartori, Patrizia, and Castiglioni, Sara
- Subjects
Magnesium ,drug resistance ,colon carcinoma ,magnesium transporters - Abstract
Chemoresistance is one of the most significant factors impeding the progress of cancer therapy (1). It is known that neoplastic cells accumulate magnesium and frequently upregulate one of its transporters, i.e.TRPM7 (2). We have investigated magnesium homeostasis in a model of chemoresistance i.e. colon carcinoma LoVo cells sensitive (LoVo-S) or resistant to doxorubicin (LoVo-R). We observed that LoVo-R have higher amount of total intracellular magnesium than LoVo-S. We studied the expression of some magnesium transporter (TRPM6, TRPM7 and MagT1) by Real Time PCR and Western Blot and found that TRPM6 and 7 are overexpressed in LoVo-S, while MagT1 is upregulated in LoVo-R. In LoVo-S, silencing TRPM7 retards cell growth and shifts the phenotype to one more similar to resistant cells. On the other hand, calpeptin, a calpain inhibitor, upregulates TRPM7, stimulated proliferation and enhances the sensitivity to doxorubicin of LoVo-R. Silencing MagT1 in LoVo-R markedly inhibited cell growth without affecting the response to doxorubicin. We conclude that alterations of magnesium homeostasis play a role in drug resistance., Italian Journal of Anatomy and Embryology, Vol. 121, No. 1 (Supplement) 2016
- Published
- 2017
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29. Burning magnesium, a sparkle in acute inflammation: gleams from experimental models.
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Castiglioni, Sara, Cazzaniga, Alessandra, Locatelli, Laura, and Maier, Jeanette A. M.
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MAGNESIUM ,INFLAMMATION ,VASCULAR diseases ,MUSIC orchestration ,MAGNESIUM group - Abstract
Magnesium contributes to the regulation of inflammatory responses. Here, we focus on the role of magnesium in acute inflammation. Although present knowledge is incomplete to delineate an accurate scenario and a schedule of the events occurring under magnesium deficiency, it emerges that low magnesium status favors the induction of acute inflammation by sensitizing sentinel cells to the noxious agent, and then by participating to the orchestration of the vascular and cellular events that characterize the process. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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30. MAGNESIUM DEFICIENCY INDUCES LIPID ACCUMULATION BY UPREGULATING EDF-1 AND PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA.
- Author
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FEDELE, Giorgia, SCRIMIERI, Roberta, ZOCCHI, Monica, CAZZANIGA, Alessandra, CASTIGLIONI, Sara, and LOCATELLI, Laura
- Subjects
PEROXISOME proliferator-activated receptors ,MEDICAL sciences ,INSULIN ,HEAT shock proteins ,MAGNESIUM ,LIPIDS ,ADIPOSE tissue physiology - Abstract
2 Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Eldor Lab, Innovation Accelerator, Consiglio Nazionale delle Ricerche, Bologna, Italy Adipose-derived stem cells (ADSCs) are one of the most promising sources for regenerative medicine. Both cell lines originate from a human colon adeno carcinoma but, when differentiated, Caco2 cells are mostly absorptive and do not secrete mucus, while HT-29 cells are a heterogeneous population, comprising scattered enterocyte elements and mucus secreting cells. [Extracted from the article]
- Published
- 2021
31. Regulation and Function of TRPM7 in Human Endothelial Cells: TRPM7 as a Potential Novel Regulator of Endothelial Function.
- Author
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Baldoli, Erika, Castiglioni, Sara, and Maier, Jeanette A. M.
- Subjects
- *
ENDOTHELIAL cells , *MAGNESIUM , *BIOLOGICAL transport , *GENE expression , *CELLULAR aging , *OXIDATIVE stress , *PHARMACOLOGY , *IMMUNOASSAY - Abstract
TRPM7, a cation channel of the transient receptor potential channel family, has been identified as a ubiquitous magnesium transporter. We here show that TRPM7 is expressed in endothelial cells isolated from the umbilical vein (HUVEC), widely used as a model of macrovascular endothelium. Quiescence and senescence do not modulate TRPM7 amounts, whereas oxidative stress generated by the addition of hydrogen peroxide increases TRPM7 levels. Moreover, high extracellular magnesium decreases the levels of TRPM7 by activating calpains, while low extracellular magnesium, known to promote endothelial dysfunction, stimulates TRPM7 accumulation partly through the action of free radicals. Indeed, the antioxidant trolox prevents TRPM7 increase by low magnesium. We also demonstrate the unique behaviour of HUVEC in responding to pharmacological and genetic inhibition of TRPM7 with an increase of cell growth and migration. Our results indicate that TRPM7 modulates endothelial behavior and that any condition leading to TRPM7 upregulation might impair endothelial function. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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32. What does magnesium have to do with COVID-19?
- Author
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Castiglioni, Sara and Maier, Jeanette A. M.
- Subjects
COVID-19 ,POST-acute COVID-19 syndrome ,MAGNESIUM ,SYMPTOMS ,CYTOKINE release syndrome ,FATIGUE (Physiology) ,MENTAL fatigue - Abstract
When Sars-CoV2 began to spread around the globe, some plausible links emerged between the pathophysiology of the infection and magnesium deficiency, which is a common, but often overlooked, finding in apparently healthy people. Initially, we noted that conditions linked to magnesium deficiency in humans, such as aging, diabetes, obesity, hypertension and cardiovascular diseases, are associated with high odds of COVID-19 mortality. Then we reasoned that Mg deficiency might contribute to crucial events in acute COVID-19, such as viral entry in the cells, endothelial dysfunction and cytokine storm. As the population of patients recovering from COVID-19 grows, a low Mg status might have a role in some symptoms of the so-called postacute COVID-19 syndrome, i.e. fatigue, brain fog, joint pain, palpitations, which result a decline in the quality of life and increase frailty. It should be recalled that magnesium deficit determines anxiety, insomnia, hyperemotionality, depression, headache, light-headedness [39], symptoms included in the post-acute COVID-19 syndrome. We conclude that monitoring and restoring magnesium homeostasis through an appropriate nutritional regimen or possibly by supplementation should be regarded as a safe and costeffective intervention that could contribute to prevent SARS-CoV-2 infection, reduce severity of COVID-19 symptoms and facilitate the recovery after the acute phase. [ABSTRACT FROM AUTHOR]
- Published
- 2021
33. BDNF and GABA-R expression is modulated in human mini-brain organoids in response to magnesium.
- Author
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Fedele, Giorgia, Castiglioni, Sara, Locatelli, Laura, Scrimieri, Roberta, Zocchi, Monica, and Cazzaniga, Alessandra
- Subjects
BLOOD-brain barrier ,MAGNESIUM ,INDUCED pluripotent stem cells ,BRAIN-derived neurotrophic factor ,ORGANOIDS - Abstract
Purpose: Mini-brain organoids 3D model represent a unique model to study neurobiology and neuropathology. Since magnesium protects against neuroinflammation and neurodegeneration, we evaluated the effects of different concentration of magnesium (Mg) salts (MgSulphate and MgPidolate) on human mini-brain organoids in the presence or not of an in vitro generated blood brain barrier (BBB). Indeed, we have previously shown that the BBB is differently permeable to distinct Mg salts. We focused on BDNF and GABA-receptors, both involved in neurodegeneration and neuroregeneration. Materials and methods: The brain-organoids were generated from human induced Pluripotent Stem cells and differentiated for 30 days. The organoids, alone or in the presence of BBB, were treated with different concentrations of MgSulphate and MgPidolate for 5 days. The expression of different neurological markers was evaluated by Real Time PCRs. The structure of organoids was evaluated by hematoxylin eosin staining and neurological markers by immuno- fluorescence. Results: Our data show that the presence of the BBB influences the expression of BDNF and GABAR in mini-brain. Indeed, high concentration of MgPidolate (5mM) upregulates only the GABAB-r when organoids are cultured without BBB. On the contrary, in the presence of BBB, a significant upregulation of BDNF and GABAR was induced by 5mM MgPidolate. No differences in the structures of organoids were detected by hematoxylin eosin staining and immunofluorescence. Conclusion: This study demonstrates that the presence of the BBB selectively changes BDNF and GABAR expression in mini-brain exposed to high concentration of MgPidolate. Because BDNF and the GABAergic system are involved in critical CNS functions, ranging from neuronal development and neuronal survival to learning and memory, these results might illuminate novel pathways explaining the neuroprotective effect of Mg. [ABSTRACT FROM AUTHOR]
- Published
- 2021
34. Crosstalk of Magnesium and Serum Lipids in Dyslipidemia and Associated Disorders: A Systematic Review.
- Author
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Găman, Mihnea-Alexandru, Dobrică, Elena-Codruța, Cozma, Matei-Alexandru, Antonie, Ninel-Iacobus, Stănescu, Ana Maria Alexandra, Găman, Amelia Maria, Diaconu, Camelia Cristina, Castiglioni, Sara, Farruggia, Giovanna, and Cappadone, Concettina
- Abstract
Dyslipidemia is a significant threat to public health worldwide and the identification of its pathogenic mechanisms, as well as novel lipid-lowering agents, are warranted. Magnesium (Mg) is a key element to human health and its deficiency has been linked to the development of lipid abnormalities and related disorders, such as the metabolic syndrome, type 2 diabetes mellitus, or cardiovascular disease. In this review, we explored the associations of Mg (dietary intake, Mg concentrations in the body) and the lipid profile, as well as the impact of Mg supplementation on serum lipids. A systematic search was computed in PubMed/MEDLINE and the Cochrane Library and 3649 potentially relevant papers were detected and screened (n = 3364 following the removal of duplicates). After the removal of irrelevant manuscripts based on the screening of their titles and abstracts (n = 3037), we examined the full-texts of 327 original papers. Finally, after we applied the exclusion and inclusion criteria, a number of 124 original articles were included in this review. Overall, the data analyzed in this review point out an association of Mg concentrations in the body with serum lipids in dyslipidemia and related disorders. However, further research is warranted to clarify whether a higher intake of Mg from the diet or via supplements can influence the lipid profile and exert lipid-lowering actions. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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35. Hypomagnesemia Is a Risk Factor for Infections after Kidney Transplantation: A Retrospective Cohort Analysis.
- Author
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Odler, Balazs, Deak, Andras T., Pregartner, Gudrun, Riedl, Regina, Bozic, Jasmin, Trummer, Christian, Prenner, Anna, Söllinger, Lukas, Krall, Marcell, Höflechner, Lukas, Hebesberger, Carina, Boxler, Matias S., Berghold, Andrea, Schemmer, Peter, Pilz, Stefan, Rosenkranz, Alexander R., Castiglioni, Sara, Farruggia, Giovanna, and Cappadone, Concettina
- Abstract
Introduction: Magnesium (Mg
2+ ) deficiency is a common finding in the early phase after kidney transplantation (KT) and has been linked to immune dysfunction and infections. Data on the association of hypomagnesemia and the rate of infections in kidney transplant recipients (KTRs) are sparse. Methods: We conducted a single-center retrospective cohort study of KTRs transplanted between 2005 and 2015. Laboratory data, including serum Mg2+ (median time of the Mg2+ measurement from KT: 29 days), rate of infections including mainly urinary tract infections (UTI), and common transplant-related viral infections (CMV, polyoma, EBV) in the early phase after KT were recorded. The primary outcome was the incidence of infections within one year after KT, while secondary outcomes were hospitalization due to infection, incidence rates of long-term (up to two years) infections, and all-cause mortality. Results: We enrolled 376 KTRs of whom 229 patients (60.9%) suffered from Mg2+ deficiency defined as a serum Mg2+ < 0.7 mmol/L. A significantly higher incidence rate of UTIs and viral infections was observed in patients with versus without Mg2+ deficiency during the first year after KT (58.5% vs. 47.6%, p = 0.039 and 69.9% vs. 51.7%, p < 0.001). After adjustment for potential confounders, serum Mg2+ deficiency remained an independent predictor of both UTIs and viral infections (odds ratio (OR): 1.73, 95% CI: 1.04–2.86, p = 0.035 and OR: 2.05, 95% CI: 1.23–3.41, p = 0.006). No group differences according to Mg2+ status in hospitalizations due to infections and infection incidence rates in the 12–24 months post-transplant were observed. In the Cox regression analysis, Mg2+ deficiency was not significantly associated with all-cause mortality (HR: 1.15, 95% CI: 0.70–1.89, p = 0.577). Conclusions: KTRs suffering from Mg2+ deficiency are at increased risk of UTIs and viral infections in the first year after KT. Interventional studies investigating the effect of Mg2+ supplementation on Mg2+ deficiency and viral infections in KTRs are needed. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
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36. Magnesium Deficiency Induces Lipid Accumulation in Vascular Endothelial Cells via Oxidative Stress—The Potential Contribution of EDF-1 and PPARγ.
- Author
-
Locatelli, Laura, Fedele, Giorgia, Castiglioni, Sara, and Maier, Jeanette A.
- Subjects
VASCULAR endothelial cells ,MAGNESIUM ,OXIDATIVE stress ,HUMAN cell culture ,REACTIVE oxygen species - Abstract
Background: Magnesium deficiency contributes to atherogenesis partly by promoting the dysfunction of endothelial cells, which are critical in vascular homeostasis and diseases. Since EDF-1 and PPARγ regulate crucial endothelial activities, we investigated the modulation of these proteins involved in lipogenesis as well the deposition of lipids in human endothelial cells cultured in different concentrations of magnesium. Methods: Human endothelial cells from the umbilical vein were cultured in medium containing from 0.1 to 5 mM magnesium for 24 h. The levels of EDF-1 and PPARγ were visualized by Western blot. Reactive oxygen species (ROS) were measured by DCFDA. Lipids were detected after O Red Oil staining. Results: Magnesium deficiency leads to the accumulation of ROS which upregulate EDF-1. Further, PPARγ is increased after culture in low magnesium, but independently from ROS. Moreover, lipids accumulate in magnesium-deficient cells. Conclusions: Our results suggest that magnesium deficiency leads to the deposition of lipids by inducing EDF-1 and PPARγ. The increase in intracellular lipids might be interpreted as an adaptive response of endothelial cells to magnesium deficiency. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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- View/download PDF
37. Magnesium Deprivation Potentiates Human Mesenchymal Stem Cell Transcriptional Remodeling
- Author
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Giovanna Farruggia, Elena Olivi, Sara Castiglioni, Jeanette A.M. Maier, Alessandra Cazzaniga, Francesca Bianchi, Concettina Cappadone, Carlo Ventura, Lucia Merolle, Emil Malucelli, Azzurra Sargenti, Stefano Iotti, Sargenti, Azzurra, Castiglioni, Sara, Olivi, Elena, Bianchi, Francesca, Cazzaniga, Alessandra, Farruggia, Giovanna, Cappadone, Concettina, Merolle, Lucia, Malucelli, Emil, Ventura, Carlo, Maier, Jeanette A. M., and Iotti, Stefano
- Subjects
0301 basic medicine ,Transcription, Genetic ,human adipose-derived mesenchymal stem cells ,Cellular differentiation ,Transcriptional remodeling ,Regenerative medicine ,Catalysi ,lcsh:Chemistry ,Osteogenesis ,Osteogenic differentiation ,Magnesium ,lcsh:QH301-705.5 ,Spectroscopy ,Regulation of gene expression ,Chemistry ,Osteogenesi ,Cell Cycle ,Cell Differentiation ,Computer Science Applications1707 Computer Vision and Pattern Recognition ,General Medicine ,Cell cycle ,Computer Science Applications ,Cell biology ,Mesenchymal Stem Cell ,Adipose Tissue ,magnesium ,human bone marrow mesenchymal stem cells ,osteogenic differentiation ,transcriptional remodeling ,Bone Marrow Cell ,Female ,Stem cell ,Reactive Oxygen Specie ,Human ,Adult ,Bone Marrow Cells ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,Humans ,Physical and Theoretical Chemistry ,Transcription factor ,Molecular Biology ,Cell growth ,Mesenchymal stem cell ,Organic Chemistry ,Mesenchymal Stem Cells ,Human bone marrow mesenchymal stem cell ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Gene Expression Regulation ,Human adipose-derived mesenchymal stem cell ,Reactive Oxygen Species - Abstract
Magnesium plays a pivotal role in energy metabolism and in the control of cell growth. While magnesium deprivation clearly shapes the behavior of normal and neoplastic cells, little is known on the role of this element in cell differentiation. Here we show that magnesium deficiency increases the transcription of multipotency markers and tissue-specific transcription factors in human adipose-derived mesenchymal stem cells exposed to a mixture of natural molecules, i.e., hyaluronic, butyric and retinoid acids, which tunes differentiation. We also demonstrate that magnesium deficiency accelerates the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. We argue that magnesium deprivation generates a stressful condition that modulates stem cell plasticity and differentiation potential. These studies indicate that it is possible to remodel transcription in mesenchymal stem cells by lowering extracellular magnesium without the need for genetic manipulation, thus offering new hints for regenerative medicine applications.
- Published
- 2018
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- View/download PDF
38. Magnesium homeostasis in colon carcinoma LoVo cells sensitive or resistant to doxorubicin
- Author
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Lucia Merolle, Giovanna Farruggia, Valentina Trapani, Stefano Iotti, Federica I. Wolf, Concettina Cappadone, Sara Castiglioni, Alessandra Cazzaniga, Jeanette A.M. Maier, Castiglioni, Sara, Cazzaniga, Alessandra, Trapani, Valentina, Cappadone, Concettina, Farruggia, Giovanna, Merolle, Lucia, Wolf, Federica I., Iotti, Stefano, and Maier, Jeanette A. M
- Subjects
medicine.medical_specialty ,Blotting, Western ,Colon carcinoma ,TRPM Cation Channels ,chemistry.chemical_element ,Cancer cell ,Cysteine Proteinase Inhibitors ,Protein Serine-Threonine Kinases ,Biology ,Article ,multidrug resistance ,Settore MED/04 - PATOLOGIA GENERALE ,Cell Line, Tumor ,Internal medicine ,medicine ,Homeostasis ,Humans ,Gene silencing ,Magnesium ,Doxorubicin ,Antibiotics, Antineoplastic ,Ion Transport ,Multidisciplinary ,Calpain ,Reverse Transcriptase Polymerase Chain Reaction ,ion channels ,Dipeptides ,Gene Expression Regulation, Neoplastic ,Endocrinology ,chemistry ,Drug Resistance, Neoplasm ,Cell culture ,Colonic Neoplasms ,Cancer research ,biology.protein ,RNA Interference ,Intracellular ,medicine.drug - Abstract
Neoplastic cells accumulate magnesium, an event which provides selective advantages and is frequently associated with TRPM7overexpression. Little is known about magnesium homeostasis in drug-resistant cancer cells. Therefore, we used the colon cancer LoVo cell model and compared doxorubicin-resistant to sensitive cells. In resistant cells the concentration of total magnesium is higher while its influx capacity is lower than in sensitive cells. Accordingly, resistant cells express lower amounts of the TRPM6 and 7, both involved in magnesium transport. While decreased TRPM6 levels are due to transcriptional regulation, post-transcriptional events are involved in reducing the amounts of TRPM7. Indeed, the calpain inhibitor calpeptin markedly increases the levels of TRPM7 in resistant cells. In doxorubicin-sensitive cells, silencing TRPM7 shifts the phenotype to one more similar to resistant cells, since in these cells silencing TRPM7 significantly decreases the influx of magnesium, increases its intracellular concentration and increases resistance to doxorubicin. On the other hand, calpain inhibition upregulates TRPM7, decreases intracellular magnesium and enhances the sensitivity to doxorubicin of resistant LoVo cells. We conclude that in LoVo cells drug resistance is associated with alteration of magnesium homeostasis through modulation of TRPM7. Our data suggest that TRPM7 expression may be an additional undisclosed player in chemoresistance.
- Published
- 2015
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