Magnesium Homeostasis Research Articles

Two central circadian oscillators OsPRR59 and OsPRR95 modulate magnesium homeostasis and carbon fixation in rice

Photosynthesis, which provides oxygen and energy for all living organisms, is circadian regulated. Photosynthesis-associated metabolism must tightly coordinate with the circadian clock to maximize the efficiency of the light-energy capture and carbon fixation. However, the molecular basis for the interplay of photosynthesis and the circadian clock is not fully understood, particularly in crop plants. Here, we report two central oscillator genes of circadian clock, OsPRR95 and OsPRR59 in rice, which function as transcriptional repressors to negatively regulate the rhythmic expression of OsMGT3 encoding a chloroplast-localized Mg2+ transporter. OsMGT3-dependent rhythmic Mg fluctuations modulate carbon fixation and consequent sugar output in rice chloroplasts. Furthermore, sugar triggers the increase of superoxide, which may act as a feedback signal to positively regulate the expression of OsPRR95 and OsPRR59. Taken together, our results reveal a negative-feedback loop that strengthens the crosstalk between photosynthetic carbon fixation and the circadian clock, which may improve plan adaptation and performance in fluctuating environments.

Ion selectivity and gating behavior of the CorA-type channel Bpss1228.

Magnesium is an essential element to sustain all forms of life. Total intracellular magnesium content is determined by the balance of magnesium influx and efflux. CorA is a divalent selective channel in the metal ion transport superfamily and is the major Mg2+ uptake pathway in prokaryotes and eukaryotic mitochondria. Previous studies have demonstrated that CorA showed distinct magnesium bound closed conformation and Mg2+-free states. In addition, CorA is regulated by cytoplasmic magnesium ions and its gating mechanism has been investigated by electron paramagnetic resonance technique and molecular dynamic simulations. Here, we report a study of the putative CorA-type channel Bpss1228 from Burkholderia pseudomallei, which has been shown to be significantly associated with pseudomallei infection. We expressed and purified the Bpss1228 in full-length. Subsequently, electrophysiological experiments further investigated the electrical characteristics of Bpss1228 and revealed that it was a strictly cation-selective channel. We also proved that Bpss1228 not only possessed magnesium-mediated regulatory property a remarkable ability to be modulated by magnesium ions. Finally, we observed the three-step gating behavior of Bpss1228 on planar lipid bilayer, and further proposed a synergistic gating mechanism by which CorA family channels control intracellular magnesium homeostasis.

The kidney reabsorption-related magnesium depletion score is associated with increased likelihood of abdominal aortic calcification among US adults.

Kidney reabsorption plays a vital role in magnesium homeostasis. This study aimed to determine the relationship between the kidney reabsorption-related magnesium depletion score (MDS) and abdominal aortic calcification (AAC). We obtained data for 2640 individuals from the National Health and Nutrition Examination Survey database and analysed the relationship between the MDS and AAC score. The MDS is a scoring system developed to predict the status of magnesium deficiency that fully considers the pathophysiological factors influencing the kidneys' reabsorption capability. AAC was quantified by the Kauppila score system based on dual-energy X-ray absorptiometry. We performed stratified analysis and multiple equation regression analysis. R and EmpowerStats were used for data analysis. A total of 2640 participants were included with the mean AAC score of 1.47±0.07. Participants with higher MDSs tended to have higher AAC scores [MDS 0: 0.75 (0.56-0.93), MDS 1: 1.02 (0.84-1.21), MDS 2: 2.34 (1.80-2.87), MDS 3: 3.19 (2.46-3.92), MDS ≥4: 4.99 (3.49-6.49)]. Compared with those with an MDS of 0, the highest subgroup (MDS ≥4) was associated with a higher AAC score {β=4.24 [95% confidence interval (CI) 2.78-5.70], P<.001} and the association was not altered [β=1.81 (95% CI 0.54-3.09), P=.002] after adjusting for numerous covariates. Subgroup analyses showed that stronger associations between the MDS and AAC score were detected in adults with lower levels of magnesium intake and older age (all P for interaction <.05). The MDS is a promising tool for identifying individuals with magnesium deficiency status who may benefit from dietary magnesium supplementation to reduce the risks of AAC.

Serum magnesium levels in chronic kidney disease patients

Objectives: Chronic kidney disease (CKD) is a condition of life-threatening nature presenting with deterioration in kidney function which is both irreversible and progressive. It is characterized by progressive incapability of the kidneys to filter the excretory products of blood consequently necessitating dialysis to prevent azotemia, end-organ damage, and ultimately death. The role of the kidneys in the homeostasis of magnesium and conservation of this neglection ion’s concentration in blood is undeniable. The objective of the present study was to estimate serum magnesium in CKD subjects and healthy control groups. Material and Methods: Serum creatinine, eGFR, Serum magnesium was assesed in 37 CKD patients and 43 healthy controls. Results: The serum creatinine levels were significantly higher (P &lt; 0.001) in cases (2.4 ± 0.88 [mg/dL]) when compared to healthy controls (0.85 ± 0.1 [mg/dL]) [Table 1]. The estimated GFR was calculated using the Modification of Diet in Renal Disease formula and was 31.2 ± 12.1 mL/min in cases and 85.67 ± 13.1 mL/min in controls and they were significantly different (P &lt; 0.001). Serum magnesium was 2.02 ± 0.36 mg/dL in cases and 2.01 ± 0.17 mg/dL in controls. Conclusion: The overall distribution showed a trend of hypomagnesemia in CKD patients but it was not statistically significant (P = 0.877). In our study, though statistically trivial, we found a trend toward hypomagnesemia in CKD patients when compared to controls. The lack of significance could be because the CKD patients were not grouped according to stages. A larger study with proper categorization and exclusion can provide us with better insights into magnesium dynamics in CKD patients.

Alterations of Serum Magnesium Concentration in Animal Models of Seizures and Epilepsy-The Effects of Treatment with a GPR39 Agonist and Knockout of the Gpr39 Gene.

Several ligands have been proposed for the GPR39 receptor, including the element zinc. The relationship between GPR39 and magnesium homeostasis has not yet been examined, nor has such a relationship in the context of seizures/epilepsy. We used samples from mice that were treated with an agonist of the GPR39 receptor (TC-G 1008) and underwent acute seizures (maximal electroshock (MES)- or 6-hertz-induced seizures) or a chronic, pentylenetetrazole (PTZ)-induced kindling model of epilepsy. MES seizures and PTZ kindling, unlike 6 Hz seizures, increased serum magnesium concentration. In turn, Gpr39-KO mice that underwent PTZ kindling displayed decreased concentrations of this element in serum, compared to WT mice subjected to this procedure. However, the levels of expression of TRPM7 and SlC41A1 proteins—which are responsible for magnesium transport into and out of cells, respectively—did not differ in the hippocampus between Gpr39-KO and WT mice. Furthermore, laser ablation inductively coupled plasma mass spectrometry applied to hippocampal slices did not reveal differences in magnesium levels between the groups. These data show the relationship between magnesium homeostasis and certain types of acute or chronic seizures (MES seizures or PTZ kindling, respectively), but do not explicitly support the role of GPR39 in mediating magnesium balance in the hippocampus in the latter model. However, decreased expression of TRPM7 and increased expression of SLC41A1—which were observed in the hippocampi of Gpr39-KO mice treated with TC-G 1008, in comparison to WT mice that received the same treatment—implicitly support the link between GPR39 and hippocampal magnesium homeostasis.

Effect of vitamin D treatment on magnesium levels in chronic hemodialysis patient; a double blind controlled clinical trial

Introduction: The homeostasis of magnesium (Mg) is impaired in chronic kidney disease (CKD) and it has been suggested that intestinal absorption of Mg may be affected by vitamin D status. 25-Hydroxy vitamin D or 25(OH)D deficiency is common in patients undergoing chronic hemodialysis; however the efficacy of nutritional vitamin D supplementation on Mg level in this population remains uncertain. Objectives: The aim of this study was to evaluate the effect of vitamin D treatment on Mg levels in chronic hemodialysis patients. Patients and Methods: This randomized clinical trial study was conducted on 69 chronic hemodialysis patients (mean age of 56.93 ±12.26 years) with serum 25-hydroxy vitamin D levels &lt;30 ng/mL. The patients were randomly assigned to one of treatment groups of oral vitamin D3- 50 000 units per week (n=35; experimental group) or 500 mg calcium D3 tablets, every 12 hours (n=34; control group) for three months. At the beginning and end of the treatment period, the levels of serum 25-hydroxy vitamin D and the levels of Mg, calcium, phosphorus and intact parathyroid hormone (iPTH) were measured in two groups. Results: In both groups, serum vitamin D levels increased significantly after treatment (P&lt;0.0001 for both groups), however after three months of treatment, in the experimental group the levels of vitamin D were significantly higher than the patients in the control group (57 ng/mL versus 28 ng/mL; P&lt;0.0001) and the median increase of vitamin D after treatment in the experimental group was significantly higher than the control group (40 ng/mL versus 10.5; P&lt;0.0001). Serum Mg levels before and after treatment were not significantly different between two groups (P=0.880 and P=0.434). In this study, we found no significant correlation between serum vitamin D level with serum Mg, calcium, phosphate, and parathyroid Hormone levels (P&gt;0.05). Conclusion: Our study shows that oral vitamin D therapy can increase 25(OH)D levels in maintenance hemodialysis patients without significant alterations in serum calcium, phosphate, magnesium and parathyroid hormone during a 12-week period. Trial Registration: Registration of trial protocol has been approved by the Iranian registry of clinical trial (#IRCT20210314050698N1; https://en.irct.ir/trial/55159, local ethical code# IR.SKUMS.REC.1397.181).

Apoptosis and (in) Pain-Potential Clinical Implications.

The deregulation of apoptosis is involved in the development of several pathologies, and recent evidence suggests that apoptosis may be involved in chronic pain, namely in neuropathic pain. Neuropathic pain is a chronic pain state caused by primary damage or dysfunction of the nervous system; however, the details of the molecular mechanisms have not yet been fully elucidated. Recently, it was found that nerve endings contain transient receptor potential (TRP) channels that sense and detect signals released by injured tissues and respond to these damage signals. TRP channels are similar to the voltage-gated potassium channels or nucleotide-gated channels that participate in calcium and magnesium homeostasis. TRP channels allowing calcium to penetrate into nerve terminals can activate apoptosis, leading to nerve terminal destruction. Further, some TRPs are activated by acid and reactive oxygen species (ROS). ROS are mainly produced in the mitochondrial respiratory chain, and an increase in ROS production and/or a decrease in the antioxidant network may induce oxidative stress (OS). Depending on the OS levels, they can promote cellular proliferation and/or cell degeneration or death. Previous studies have indicated that proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), play an important role in the peripheral mediation of neuropathic pain. This article aims to perform a review of the involvement of apoptosis in pain, particularly the role of OS and neuroinflammation, and the clinical relevance of this knowledge. The potential discovery of new biomarkers and therapeutic targets can result in the development of more effective and targeted drugs to treat chronic pain, namely neuropathic pain. Highlights: Oxidative stress and neuroinflammation can activate cell signaling pathways that can lead to nerve terminal destruction by apoptosis. These could constitute potential new pain biomarkers and targets for therapy in neuropathic pain.

Comparative transcriptome analysis revealed the role and mechanism of a FeoC-like LuxR-type regulator in intracellular survival of Aeromonas hydrophila

A. hydrophila is one of the most important pathogens in the aquaculture industry, and its drug-resistant strains continue to emerge due to the irregular use of drugs. Previous studies found A. hydrophila could survive in fish macrophages, so it was speculated that A. hydrophila may hide in host macrophages to escape the killing of drugs and other antibacterial factors. The mechanism of A. hydrophila survival in fish macrophages is worthy of further study. In this study, the expression of a FeoC-like LuxR-type regulator was stable silenced by shRNA to construct the silencing strain feoC-RNAi. And the intracellular survival rate of feoC-RNAi decreased by about 67.5% compared with that of the wild-type strain. Comprehensive transcriptome analysis suggested that this FeoC-like LuxR-type regulator may regulate at least 1286 genes. According to GO and KEGG analysis of these 1286 DEGs, it can be speculated that this regulator may affect A. hydrophila intracellular survival by regulating bacterial metal ion metabolism, chemotaxis, type IV pilus biogenesis and binding, then further regulate the bacterial intracellular survival. Further comparison on biological phenotype of A. hydrophila B11 and feoC-RNAi revealed this FeoC-like LuxR-type regulator could regulate the expression of genes related to iron and magnesium metabolism and greatly affect bacterial growth under the limited magnesium concentration, but has no effect on bacterial growth under the limited iron concentration. And inhibited expression of this FeoC-like LuxR-type regulator led to a decrease in chemotactic ability of A. hydrophila by about 60%, disappearance of pilus, and a decrease in adhesion by about 50%. So a conclusion could be made that this FeoC-like LuxR-type regulator might play a vital role in regulating the uptake of magnesium and the homeostasis of magnesium and iron, and chemotaxis, type IV pilus biogenesis and adhesion of A. hydrophila, then further protect bacteria from the microbicidal actions and keep survival in host macrophages.

31 P MRSI at 7 T enables high-resolution volumetric mapping of the intracellular magnesium ion content in human lower leg muscles.

The non-invasive determination of the free magnesium ion concentration ([Mg2+free ]) using 31 P MRSI in vivo is of interest in research on various pathologies, e.g. diabetes. The purpose of this study was to demonstrate the potential of 31 P MRSI at 7 T to enable volumetric, high-resolution mapping of [Mg2+free ]. 3D 31 P MRSI datasets from the lower leg of three healthy volunteers were acquired at B0 = 7 T with a nominal spatial resolution of (8× 8× 16)mm3 in 56 min. Volumetric [Mg2+free ] maps were calculated based on the quantified local chemical shift difference between the α- and β-resonance of adenosine triphosphate (ATP) considering also local pH values. Mean [Mg2+free ] values from three different muscle groups were compared. To demonstrate the potential of reducing the measurement time, the analysis was repeated on the acquired MRSI data retrospectively reconstructed with fewer averages. The generated [Mg2+free ] maps revealed local differences, and mean [Mg2+free ] values of (1.08 ± 0.03)mM were found in the tibialis anterior, (0.91 ± 0.04)mM in the soleus and (0.98 ± 0.03)mM in the gastrocnemius medialis. The time-reduced 28-min scan resulted in comparable [Mg2+free ] maps, and mean values being in agreement with the values from the 56-min scan. 31 P MRSI at 7 T enables volumetric, high-resolution mapping of free magnesium ion content in human lower leg muscles. The measurement time of the 31 P MRSI acquisition can be reduced to 28 min, opening the potential to apply volumetric [Mg2+free ] mapping for the investigation of pathologies with altered magnesium homeostasis.

332 Association of sphingolipid de novo synthesis with airway response to magnesium

OBJECTIVES/GOALS: MgSO4 is a frequently used to treat asthma exacerbations. Its role in the management of pediatric asthma remains controversial. Our objective is to demonstrate that the response of the small (peripheral) airways depends on airway de novo sphingolipid synthesis, clinically and experimentally. The small airways are the main site of asthma pathology. METHODS/STUDY POPULATION: We investigated airway reactivity in response to MgSO4 in murine small airways and children 1. Precision-cut lung slices (PCLS): Using heterozygous knockouts mice of one of the Sptlc2 subunit of the serine palmitoyl-CoA transferase (SPT) which results in reduced tissue sphingolipid levels compared to wild-type control littermates (Sptlc2+/+). We compared small airway dilation to MgSO4 in Sptlc2+/- and Sptlc2+/+ mice. This was assessed by directly visualization of small airway contractility in PCLS from Sptlc2+/- mice using video phase-contrast microscopy 2. Clinical response to MgSO4 in children by using a respiratory score before and after the treatment. The response to MgSO4 was the correlated to asthma-associated 17q21 specific single nucleotide polymorphisms (SNPs) from DNA isolated from buccal swabs RESULTS/ANTICIPATED RESULTS: Sphingolipid-mediated activity alters magnesium response in small airways. We assessed whether downregulation of SPT could lead to alterations in MgSO4-induced small airway dilation and in MgSO4 responsiveness in mouse tracheal rings and found that the magnesium-induced relaxation of airways pre-contracted with methacholine was impaired in Sptlc+/- mice compared to the control group (p=&lt;0.05) Clinical response to MgSO4 in children with status asthmaticus. A respiratory score was assessed in a cohort of 5 to 21-year-old who received IV MgSO4. An increase of 3 or more points was considered positive. Only 32% of the patients showed a favorable improvement to the medication, showing variability of response between individuals. The correlation of sphingolipid-deficient SNPs and MgSO4 responsiveness is ongoing DISCUSSION/SIGNIFICANCE: This suggest that decreased SPT activity in the respiratory track alters the response of the airways to magnesium. Connecting decreased de novo SL synthesis to alterations in cellular magnesium homeostasis provides a mechanistic link to differential airway reactivity to MgSO4 in pediatric asthma management.

A Central Role for Magnesium Homeostasis during Adaptation to Osmotic Stress.

ABSTRACTOsmotic stress is a significant physical challenge for free-living cells. Cells from all three domains of life maintain viability during osmotic stress by tightly regulating the major cellular osmolyte potassium (K+) and by import or synthesis of compatible solutes. It has been widely established that in response to high salt stress, many bacteria transiently accumulate high levels of K+, leading to bacteriostasis, with growth resuming only when compatible solutes accumulate and K+ levels are restored to biocompatible levels. Using Bacillus subtilis as a model system, we provide evidence that K+ fluxes perturb Mg2+ homeostasis: import of K+ upon osmotic upshift is correlated with Mg2+ efflux, and Mg2+ reimport is critical for adaptation. The transient growth inhibition resulting from hyperosmotic stress is coincident with loss of Mg2+ and a decrease in protein translation. Conversely, the reimport of Mg2+ is a limiting factor during resumption of growth. Furthermore, we show the essential signaling dinucleotide cyclic di-AMP fluctuates dynamically in coordination with Mg2+ and K+ levels, consistent with the proposal that cyclic di-AMP orchestrates the cellular response to osmotic stress.

Evolution of Transient Receptor Potential (TRP) Ion Channels in Antarctic Fishes (Cryonotothenioidea) and Identification of Putative Thermosensors.

Animals rely on their sensory systems to inform them of ecologically relevant environmental variation. In the Southern Ocean, the thermal environment has remained between −1.9 and 5 °C for 15 Myr, yet we have no knowledge of how an Antarctic marine organism might sense their thermal habitat as we have yet to discover a thermosensitive ion channel that gates (opens/closes) below 10 °C. Here, we investigate the evolutionary dynamics of transient receptor potential (TRP) channels, which are the primary thermosensors in animals, within cryonotothenioid fishes—the dominant fish fauna of the Southern Ocean. We found cryonotothenioids have a similar complement of TRP channels as other teleosts (∼28 genes). Previous work has shown that thermosensitive gating in a given channel is species specific, and multiple channels act together to sense the thermal environment. Therefore, we combined evidence of changes in selective pressure, gene gain/loss dynamics, and the first sensory ganglion transcriptome in this clade to identify the best candidate TRP channels that might have a functional dynamic range relevant for frigid Antarctic temperatures. We concluded that TRPV1a, TRPA1b, and TRPM4 are the likeliest putative thermosensors, and found evidence of diversifying selection at sites across these proteins. We also put forward hypotheses for molecular mechanisms of other cryonotothenioid adaptations, such as reduced skeletal calcium deposition, sensing oxidative stress, and unusual magnesium homeostasis. By completing a comprehensive and unbiased survey of these genes, we lay the groundwork for functional characterization and answering long-standing thermodynamic questions of thermosensitive gating and protein adaptation to low temperatures.

Magnesium Homeostasis in Myogenic Differentiation-A Focus on the Regulation of TRPM7, MagT1 and SLC41A1 Transporters.

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.

Insight into the mechanism of indium toxicity in rice

Indium is widely used in the technology industry and is an emerging form of environmental pollution. The presence of indium in soil and groundwater inhibits shoot and root growth in crops, thus reducing yields. However, the underlying mechanisms are unknown, making it difficult to design effective countermeasures. We explored the spatiotemporal effects of excess indium on the morphological, physiological and biochemical properties of rice (Oryza sativa L.). Indium accumulated mainly in the roots, severely restricting their growth and causing the acute perturbation of phosphorus, magnesium and iron homeostasis. Other effects included leaf necrosis and anatomical changes in the roots (thinned sclerenchyma and enlarged epidermal and exodermal layers). Whole-transcriptome sequencing revealed that rice immediately responded to indium stress by activating genes involved in heavy metal tolerance and phosphate starvation responses, including the expression of genes encoding phosphate-regulated transcription factors and transporters in the roots. Direct indium toxicity rather than phosphate deficiency was identified as the major factor affecting the growth of rice plants, resulting in the profound phenotypic changes we observed. The application of exogenous phosphate alleviated indium toxicity by reducing indium uptake. Our results suggest that indium immobilization could be used to prevent indium toxicity in the field.

A metal tolerance protein, MTP10, is required for the calcium and magnesium homeostasis in Arabidopsis

ABSTRACT Nutrient antagonism typically refers to the fact that too high a concentration of one nutrient inhibits the absorption of another nutrient. In plants, Ca2+ (Calcium) and Mg2+ (Magnesium) are the two most abundant divalent cations, which are known to have antagonistic interactions. Hence, maintaining their homeostasis is crucial for plant growth and development. In this study, we showed that MTP10 (Metal Tolerance Protein 10) is an important regulator for maintaining homeostasis of Mg and Ca in Arabidopsis. The mtp10 mutant displayed severe growth retardation in the presence of excess Mg2+, to which the addition of Ca2+ was able to rescue the phenotype of mtp10 mutant. Additionally, the deficiency of Ca2+ in the culture medium accelerated the high-Mg sensitivity of the mtp10 mutant. The yeast complementation assay suggested that AtMTP10 had no Ca2+ transport activity. And the ICP-MS data further confirmed the antagonistic relationship between Ca2+ and Mg2+, with the addition of Ca2+ reducing the excessive accumulation of Mg2+ and high-Mg inhibiting the uptake of Ca2+. We conclude that the Arabidopsis MTP10 is essential for the regulation of Mg and Ca homeostasis.

A potential protective role of magnesium in neuroCOVID

Several recent studies support a role of dysregulated magnesium homeostasis in COVID-19. In the present narrative review, we focus on the neurological aspects of this disease, collectively known as neuroCOVID, and we propose some mechanisms by which alterations of magnesium may contribute to the involvement of the nervous system in the context of SARS-CoV-2 infection. Further fundamental, translational, and clinical research is needed to underpin the potential relationships between altered magnesium status and neuro-COVID, with potentially novel therapeutic implications.

Phospholipase Dα1 Acts as a Negative Regulator of High Mg2+-Induced Leaf Senescence in Arabidopsis.

Magnesium (Mg2+) is a macronutrient involved in essential cellular processes. Its deficiency or excess is a stress factor for plants, seriously affecting their growth and development and therefore, its accurate regulation is essential. Recently, we discovered that phospholipase Dα1 (PLDα1) activity is vital in the stress response to high-magnesium conditions in Arabidopsis roots. This study shows that PLDα1 acts as a negative regulator of high-Mg2+-induced leaf senescence in Arabidopsis. The level of phosphatidic acid produced by PLDα1 and the amount of PLDα1 in the leaves increase in plants treated with high Mg2+. A knockout mutant of PLDα1 (pldα1-1), exhibits premature leaf senescence under high-Mg2+ conditions. In pldα1-1 plants, higher accumulation of abscisic and jasmonic acid (JA) and impaired magnesium, potassium and phosphate homeostasis were observed under high-Mg2+ conditions. High Mg2+ also led to an increase of starch and proline content in Arabidopsis plants. While the starch content was higher in pldα1-1 plants, proline content was significantly lower in pldα1-1 compared with wild type plants. Our results show that PLDα1 is essential for Arabidopsis plants to cope with the pleiotropic effects of high-Mg2+ stress and delay the leaf senescence.

Effect of Dapagliflozin and Magnesium Supplementation on Renal Magnesium Handling and Magnesium Homeostasis in Metabolic Syndrome.

The prevalence of metabolic syndrome (MetS) is increasing, and patients with MetS are at an increased risk of cardiovascular disease and diabetes. There is a close link between hypomagnesemia and MetS. Administration of sodium-glucose transporter 2 (SGLT2) inhibitors has been reported to increase serum magnesium levels in patients with diabetes. We investigated the alterations in renal magnesium handling in an animal model of MetS and analyzed the effects of SGLT2 inhibitors. Adult rats were fed a fructose-rich diet to induce MetS in the first 3 months and were then treated with either dapagliflozin or magnesium sulfate-containing drinking water for another 3 months. Fructose-fed animals had increased insulin resistance, hypomagnesemia, and decreased urinary magnesium excretion. Dapagliflozin treatment improved insulin resistance by decreasing glucose and insulin levels, increased serum magnesium levels, and reduced urinary magnesium excretion. Serum vitamin D and parathyroid hormone levels were decreased in fructose-fed animals, and the levels remained low despite dapagliflozin and magnesium supplementation. In the kidney, claudin-16, TRPM6/7, and FXDY expression was increased in fructose-fed animals. Dapagliflozin increased intracellular magnesium concentration, and this effect was inhibited by TRPM6 blockade and the EGFR antagonist. We concluded that high fructose intake combined with a low-magnesium diet induced MetS and hypomagnesemia. Both dapagliflozin and magnesium sulfate supplementation improved the features of MetS and increased serum magnesium levels. Expression levels of magnesium transporters such as claudin-16, TRPM6/7, and FXYD2 were increased in fructose-fed animals and in those administered dapagliflozin and magnesium sulfate. Dapagliflozin enhances TRPM6-mediated trans-epithelial magnesium transport in renal tubule cells.

Cyclin M2 (CNNM2) Is Essential for Development and Systemic Magnesium Homeostasis

Cyclin M2 (CNNM2) Is Essential for Development and Systemic Magnesium Homeostasis

Гіпомагніємія при хронічній хворобі нирок: проблема чи індивідуальні особливості окремих хворих?

У статті розглянуто проблему дефіциту магнію у пацієнтів із хронічною хворобою нирок (ХХН). Вона потребує особливої уваги з боку клініцистів у зв’язку з підвищеним ризиком розвитку серцево-судинних ускладнень. Під час дослідження було виявлено, що третина пацієнтів із ХХН І–ІІІ стадій має дефіцит магнію. Застосування препаратів магнію дозволяє нормалізувати магнієвий статус.