Enhanced sodium-dependent extrusion of magnesium in mutant cells established from a mouse renal tubular cell line

Watanabe, Masaru; Konishi, Masato; Ohkido, Ichiro; Matsufuji, Senya

doi:10.1152/ajprenal.00091.2005

Cited by 12 publications

(9 citation statements)

References 21 publications

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“…In agreement with our results, Mg extrusion in a Na-containing, Mg-free medium was negligible in control NRK-52E cells but significant in high-Mg cultured cells. An enhanced Na + /Mg 2+ exchanger activity was also observed in a mutant cell line from mouse cortical tubular cells that were selected to grow in media with an extremely high [Mg] of 100 mM [38]. However, the reasons for these changes have not been identified in these studies.…”

Section: Discussionmentioning

confidence: 94%

Rumen epithelial cells adapt magnesium transport to high and low extracellular magnesium conditions

Schweigel

Kuzinski²,

Deiner³

et al. 2009

Magnesium Research

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A protein of~70-kDa was identified as a candidate Na + /Mg 2+ exchanger in rumen epithelial cells (REC). Melastatin-related Transient Receptor Potential 7 (TRPM7) and Magnesium Transporter 1 (MagT1) transcripts and, from them, encoded proteins were also detected. The regulation of these Mg transport pathways by extracellular [Mg] changes was the main focus of this study. Therefore, a 24-h pre-incubation of ovine REC in control (1.2 mM), low (0.12 mM)-Mg, and high (5 mM)-Mg medium was performed. Na + /Mg 2+ exchangers, TRPM7 and MagT1 abundance and activity were investigated by Western blot analysis, flow cytometry, immunocytochemistry and fluorescence spectroscopic measurements of [Mg 2+ ] i changes. Inhibitors were employed to differentiate Na + /Mg 2+ exchanger-mediated (imipramine) and channel-mediated (cobalt(III)hexaammine, nitrendipine) Mg transport. Basal [Mg 2+ ] i (0.40 ± 0.02 mM) was not influenced by pre-incubation in low-or high-Mg medium. However, compared with control REC (4.1 ± 0.7 μM/min), such cells showed reduced (2.8 ± 0.6 μM/min) or elevated (6.4 ± 0.9 μM/min) Mg extrusion rates that correlated with a decreased (25%) and increased (38%) expression of the putative Na + /Mg 2+ exchanger protein, respectively. Low-and high-Mg pre-incubated REC were both characterized by an increased (30-40%) influx capacity. In low-Mg REC, the latter resulted mainly from a strong activation of the TRPM7-related transport component. The data thus clearly demonstrate the intrinsic regulation of REC transmembrane Mg transport.

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Section: Discussionmentioning

confidence: 94%

Rumen epithelial cells adapt magnesium transport to high and low extracellular magnesium conditions

Schweigel

Kuzinski²,

Deiner³

et al. 2009

Magnesium Research

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“…All approaches used so far, for example, the establishment of a high (Ͼ100 mM) Mg 2ϩ -resistant cell line (48), have failed. Also, with the exception of hSLC41A1, all new candidate Mg 2ϩ transporters found by genetic screening seem to mediate Mg 2ϩ uptake (10,30,35,52).…”

Section: Discussionmentioning

confidence: 99%

“…Although not selective, these are the current pharmacological agents of choice for manipulating the Na ϩ /Mg 2ϩ exchanger functional activity (1,14,38,52). In a majority of studies (14,17,37,48,52), a Ϸ50% inhibition of Mg 2ϩ efflux has been reported after the application of imipramine (100 to 500 M). In this study, the inhibitory effect of imipramine (Ϫ88%) is in the order of that Na ϩ withdrawal (Ϫ91%), and quinidine has even led to a complete block of hSLC41A1-related Mg 2ϩ extrusion.…”

Section: Discussionmentioning

confidence: 99%

Human gene SLC41A1 encodes for the Na⁺/Mg²⁺ exchanger

Kolísek

Nestler

Vormann³

et al. 2012

American Journal of Physiology-Cell Physiology

117

164

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Magnesium (Mg(2+)), the second most abundant divalent intracellular cation, is involved in the vast majority of intracellular processes, including the synthesis of nucleic acids, proteins, and energy metabolism. The concentration of intracellular free Mg(2+) ([Mg(2+)](i)) in mammalian cells is therefore tightly regulated to its optimum, mainly by an exchange of intracellular Mg(2+) for extracellular Na(+). Despite the importance of this process for cellular Mg(2+) homeostasis, the gene(s) encoding for the functional Na(+)/Mg(2+) exchanger is (are) still unknown. Here, using the fluorescent probe mag-fura 2 to measure [Mg(2+)](i) changes, we examine Mg(2+) extrusion from hSLC41A1-overexpressing human embryonic kidney (HEK)-293 cells. A three- to fourfold elevation of [Mg(2+)](i) was accompanied by a five- to ninefold increase of Mg(2+) efflux. The latter was strictly dependent on extracellular Na(+) and reduced by 91% after complete replacement of Na(+) with N-methyl-d-glucamine. Imipramine and quinidine, known unspecific Na(+)/Mg(2+) exchanger inhibitors, led to a strong 88% to 100% inhibition of hSLC41A1-related Mg(2+) extrusion. In addition, our data show regulation of the transport activity via phosphorylation by cAMP-dependent protein kinase A. As these are the typical characteristics of a Na(+)/Mg(2+) exchanger, we conclude that the human SLC41A1 gene encodes for the Na(+)/Mg(2+) exchanger, the predominant Mg(2+) efflux system. Based on this finding, the analysis of Na(+)/Mg(2+) exchanger regulation and its involvement in the pathogenesis of diseases such as Parkinson's disease and hypertension at the molecular level should now be possible.

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“…Tumour cells proved to be the most resistant cell type; for example, HL-60 leukaemia cells, MCF7 mammary carcinoma and Ehrlich ascites tumour cells had an unaltered growth rate at 0.05 mmol/l extracellular Mg [9,19]. However, every cell strain can adapt to non-physiological concentrations of extracellular Mg, as shown by the case of chronic adaptation to very high or very low Mg-containing medium [14,20].…”

Section: Figure 1 Pathway Of Cell Proliferation and Its Regulation By Mgmentioning

confidence: 99%

Cell (patho)physiology of magnesium

2007

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There is an unsettled debate about the role of magnesium as a 'chronic regulator' of biological functions, as opposed to the well-known role for calcium as an 'acute regulator'. New and old findings appear to delineate an increasingly complex and important role for magnesium in many cellular functions. This review summarizes the available evidence for a link between the regulation of intracellular magnesium availability and the control of cell growth, energy metabolism and death, both in healthy and diseased conditions. A comprehensive view is precluded by technical difficulties in tracing magnesium within a multicompartment and dynamic environment like the cell; nevertheless, the last few years has witnessed encouraging progress towards a better characterization of magnesium transport and its storage or mobilization inside the cell. The latest findings pave the road towards a new and deeper appreciation of magnesium homoeostasis and its role in the regulation of essential cell functions.

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Enhanced sodium-dependent extrusion of magnesium in mutant cells established from a mouse renal tubular cell line

Cited by 12 publications

References 21 publications

Rumen epithelial cells adapt magnesium transport to high and low extracellular magnesium conditions

Rumen epithelial cells adapt magnesium transport to high and low extracellular magnesium conditions

Human gene SLC41A1 encodes for the Na⁺/Mg²⁺ exchanger

Cell (patho)physiology of magnesium

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Enhanced sodium-dependent extrusion of magnesium in mutant cells established from a mouse renal tubular cell line

Cited by 12 publications

References 21 publications

Rumen epithelial cells adapt magnesium transport to high and low extracellular magnesium conditions

Rumen epithelial cells adapt magnesium transport to high and low extracellular magnesium conditions

Human gene SLC41A1 encodes for the Na+/Mg2+ exchanger

Cell (patho)physiology of magnesium

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Product

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Human gene SLC41A1 encodes for the Na⁺/Mg²⁺ exchanger