Article: Sodium Citrate Increases Expression and Flux of Mg<sup>2+</sup> Transport Carriers Mediated by Activation of MEK/ERK/c-Fos Pathway in Renal Tubular Epithelial Cells
Nutrients. 2018 Sept. 20, v. 10, no. 10
2018
Abstract: ... increases TRPM6 expression and Mg2+ influx mediated by the activation of NADPH oxidase and an EGFR/ERK/c-Fos ... of TRPM6 and CNNM2 in renal tubular epithelial NRK-52E cells. The SC-induced elevation of TRPM6 was ... increased the levels of p-ERK1/2 and p-c-Fos, which were inhibited by U0126. SC induced alkalization ...
| Abstract | A chronic magnesium deficiency may be one of the causes of lifestyle-related diseases such as hypertension and diabetes. Serum Mg2+ concentration is strictly controlled by the reabsorption pathway in the renal tubules, but little is known about how Mg2+ reabsorption is upregulated. We searched for food compounds which can increase the expression levels of Mg2+ transport carriers including transient receptor potential melastatin 6 (TRPM6) channel and cyclin M2 (CNNM2). Sodium citrate (SC) increased the mRNA levels of TRPM6 and CNNM2 in renal tubular epithelial NRK-52E cells. The SC-induced elevation of TRPM6 was inhibited by U0126, a mitogen-activated protein kinase kinase (MEK) inhibitor, but the CNNM2 was not. SC increased the levels of p-ERK1/2 and p-c-Fos, which were inhibited by U0126. SC induced alkalization of culture medium. Both SC and alkalization enhanced Mg2+ influx, which was inhibited by U0126 and introduction of TRPM6 siRNA. The reporter activity of TRPM6 was increased by SC and alkalization, which was suppressed by mutation in an AP-1-binding site. The SC-induced elevation of p-ERK1/2 and p-EGFR was inhibited by diphenylene iodonium, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, and erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. SC did not change the level of acetyl histone H3, but increased the association of c-Fos with the promoter region of TRPM6. These results suggest that SC increases TRPM6 expression and Mg2+ influx mediated by the activation of NADPH oxidase and an EGFR/ERK/c-Fos pathway in the renal tubules. |
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| Keywords | NAD(P)H oxidase (H2O2-forming) ; NADP (coenzyme) ; alkalinization ; blood serum ; culture media ; cyclins ; diabetes ; enzyme inhibitors ; epidermal growth factor receptors ; epithelial cells ; epithelium ; histones ; hypertension ; magnesium ; messenger RNA ; mitogen-activated protein kinase kinase ; mutation ; nutrient deficiencies ; promoter regions ; renal tubules ; resorption ; small interfering RNA ; sodium citrate ; tyrosine |
| Language | English |
| Dates of publication | 2018-0920 |
| Publishing place | Multidisciplinary Digital Publishing Institute |
| Document type | Article |
| ZDB-ID | 2518386-2 |
| ISSN | 2072-6643 |
| ISSN | 2072-6643 |
| DOI | 10.3390/nu10101345 |
| Database | NAL-Catalogue (AGRICOLA) |
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