Angiotensin II Type I Receptor Modulates Intracellular Free Mg2+ in Renally Derived Cells via Na+-dependent Ca2+-independent Mechanisms

Touyz, Rhian M.; Mercure, Chantal; Reudelhuber, Timothy L.

doi:10.1074/jbc.m008101200

Cited by 26 publications

(23 citation statements)

References 47 publications

(34 reference statements)

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“…This is consistent with the concept that either Mg 2ϩ or K ϩ can compete for Na ϩ binding. Measurements of free Mg 2ϩ in cultured renal cells are in the range we used (67,68), but free Mg 2ϩ in skeletal, cardiac, and smooth muscle cells is as high as 1 mM (69).…”

Section: Discussionmentioning

confidence: 97%

Differential Regulation of Renal Na,K-ATPase by Splice Variants of the γ Subunit

Arystarkhova

Donnet

Asinovski

et al. 2002

Journal of Biological Chemistry

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Sodium and potassium-exchanging adenosine triphosphatase (Na,K-ATPase) in the kidney is associated with the ␥ subunit (␥, FXYD2), a single-span membrane protein that modulates ATPase properties. Rat and human ␥ occur in two splice variants, ␥a and ␥b, with different N termini. Here we investigated their structural heterogeneity and functional effects on Na,K-ATPase properties. Both forms were post-translationally modified during in vitro translation with microsomes, indicating that there are four possible forms of ␥. Site-directed mutagenesis revealed Thr 2 and Ser 5 as potential sites for post-translational modification. Similar modification can occur in cells, with consequences for Na,K-ATPase properties. We showed previously that stable transfection of ␥a into NRK-52E cells resulted in reduction of apparent affinities for Na ؉ and K ؉ . Individual clones differed in ␥ post-translational modification, however, and the effect on Na ؉ affinity was absent in clones with full modification. Here, transfection of ␥b also resulted in clones with or without post-translational modification. Both groups showed a reduction in Na ؉ affinity, but modification was required for the effect on K ؉ affinity. There were minor increases in ATP affinity. The physiological importance of the reduction in Na ؉ affinity was shown by the slower growth of ␥a, ␥b, and ␥b transfectants in culture. The differential influence of the four structural variants of ␥ on affinities of the Na,KATPase for Na ؉ and K ؉ , together with our previous finding of different distributions of ␥a and ␥b along the rat nephron, suggests a highly specific mode of regulation of sodium pump properties in kidney.

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Section: Discussionmentioning

confidence: 97%

Differential Regulation of Renal Na,K-ATPase by Splice Variants of the γ Subunit

Arystarkhova

Donnet

Asinovski

et al. 2002

Journal of Biological Chemistry

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“…Few studies have investigated the effects of Mg deficiency on the hormonal systems that control blood pressure. Angiotensin II decreases intracellular Mg in a dose-dependent manner, and this effect is inhibited by angiotensin II receptor blockers (ARBs) [18]. Mg deficiency may promote an angiotensin II-induced rise in blood pressure, aldosterone concentration, and vasoconstrictive prostaglandins [19].…”

Section: Introductionmentioning

confidence: 99%

Additional antihypertensive effect of magnesium supplementation with an angiotensin II receptor blocker in hypomagnesemic rats

Jin

Kim

et al. 2013

Korean J Intern Med

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Background/AimsMagnesium (Mg) is an essential element for vascular function and blood pressure regulation. Several studies have demonstrated that Mg concentration is inversely associated with blood pressure, and that Mg supplementation attenuates hypertension. The purpose of this study was to evaluate the effect of dietary Mg supplementation on the blood pressure effects of an angiotensin II receptor blocker (ARB) in hypomagnesemic rats.MethodsFifty male Sprague-Dawley rats were randomly divided into Mg-deficient (n = 30), normal diet plus Mg (n = 10), and control groups (n = 10). Mg-free, high-Mg, and normal-Mg diets were respectively fed to the rats. After 14 weeks, 10 of the 30 Mg-deficient rats were treated with Mg, 10 Mg-deficient rats received an ARB, and 10 Mg-deficient rats received an ARB plus Mg for 4 weeks.ResultsSystolic blood pressure was significantly higher in the Mg-deficient rats than in the control rats at week 14. Hypomagnesemic rats exhibited decreased systolic blood pressure after treatment with Mg, and systolic blood pressure showed a greater decrease after ARB treatment. Treatment with the ARB/Mg combination resulted in the greatest decrease in systolic blood pressure. Mg deficiency did not affect the serum angiotensin II level, but did increase the serum aldosterone concentration. Concomitant Mg/ARB supplementation significantly decreased the elevated serum aldosterone level in hypomagnesemic rats. Kidney tissues of the hypomagnesemic rats revealed mild to moderate inflammatory infiltrates. Mg and/or ARB treatment did not reverse the inflammatory reaction in the kidneys of hypomagnesemic rats.ConclusionsConcurrent dietary Mg supplementation can enhance ARB-induced blood pressure reduction in rats with hypomagnesemic hypertension.

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“…Ang II stimulates vascular contraction, growth, and inflammation, in part through Mg 2ϩ -dependent processes. 39,44 Aldosterone, a mineralocorticoid hormone that influences cellular Mg 2ϩ metabolism, 45,46 is increasingly being recognized as an important modulator of vascular function. 47,48 In this study, we demonstrate that Ang II and aldosterone regulate TRPM7 mRNA and protein content.…”

Section: Mgmentioning

confidence: 99%

Transient Receptor Potential Melastatin 7 Ion Channels Regulate Magnesium Homeostasis in Vascular Smooth Muscle Cells

He¹,

Yao²,

Savoia³

et al. 2005

Circulation Research

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179

165

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Abstract-Magnesium modulates vascular smooth muscle cell (VSMC) function. However, molecular mechanisms regulating VSMC Mg 2ϩ remain unknown. Using biochemical, pharmacological, and genetic tools, the role of transient receptor potential membrane melastatin 7 (TRPM7) cation channel in VSMC Mg 2ϩ homeostasis was evaluated. Rat, mouse, and human VSMCs were studied. Reverse transcriptase polymerase chain reaction and immunoblotting demonstrated TRPM7 presence in VSMCs (membrane and cytosol). Angiotensin II (Ang II) and aldosterone increased TRPM7 expression. Gene silencing using small interfering RNA (siRNA) against TRPM7, downregulated TRPM7 (mRNA and protein). Basal [1][2][3][4] Mg 2ϩ also influences growth processes associated with remodeling and fibrosis, characteristic features of vascular damage in hypertension, atherosclerosis, and diabetes. 5,6 At the subcellular level, these effects occur, at least in part, through Mg 2ϩ -dependent regulation of mitogen-activated protein (MAP) kinases, tyrosine kinases, and reactive oxygen species, important signaling molecules involved in VSMC proliferation, fibrosis, and inflammation. [7][8][9] Microarray studies demonstrated that changes in [Mg 2ϩ ] i have potent modulatory actions on expression of various growth signaling molecules. 10 polypeptides with dual-function ion channel/ protein kinases, characterized by six transmembrane spanning domains with an adjacent coiled coil region, a long, highly conserved cytoplasmic N-terminal region, and a cytoplasmic C terminus, which has enzymatic activity. 22-24 TRPM6 and TRPM7, which have an overall amino acid sequence homology of 52%, harbor serine/threonine kinase domains in their C termini. 21,25,26 TRPM6 is preferentially expressed in small intestine, colon, and kidney, participating in gastrointestinal and renal Mg 2ϩ absorption. 21,27,28 Mutations in TRPM6 cause hypomagnesemia with secondary hypocalcemia. 27,29,30 Expression of TRPM7 is widespread with transcripts in brain, spleen, lung, kidney, heart, and liver. 22,[31][32][33] It is also expressed in lymphoid-derived cell lines, hematopoietic cells, granulocytes, leukemia cells, and microglia. 20,25 In various cell lines, TRPM7 is regulated by intracellular levels of Mg-ATP and is strongly activated when Mg-ATP falls below 1 mmol/L. 32,34 Studies in microglial and HEK293-transfected cells demonstrated that TRPM7 activity is also modulated through its endogenous kinase in a cAMP-, PKA-, and Src-dependent manner 25,35 and is inactivated by PIP2 hydrolysis in cardiac fibroblasts. 36 To our knowledge nothing is known about the status of TRPM7 in the vasculature. It is unclear whether this cation channel influences Mg 2ϩ transport in vascular cells and whether vasoactive agents regulate TRPM7. To gain insights into the putative role of TRPM7 in vascular Mg 2ϩ homeostasis, we used a combination of biochemical, pharmacological, molecular and genetic approaches to investigate the presence and functional significance of TRPM7 in VSMCs. Our data demonstrate that VSMCs poss...

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Angiotensin II Type I Receptor Modulates Intracellular Free Mg2+ in Renally Derived Cells via Na+-dependent Ca2+-independent Mechanisms

Abstract: Treatment of Madin-Darby canine kidney (MDCK)cellsis an essential cofactor for many enzymes, it modulates various transporters and ion channels, it regulates lipid-and phosphoinositide-derived second messengers, and it influences DNA and protein synthesis (1)(2)(3)(4)(5)

Cited by 26 publications

References 47 publications

Differential Regulation of Renal Na,K-ATPase by Splice Variants of the γ Subunit

Differential Regulation of Renal Na,K-ATPase by Splice Variants of the γ Subunit

Additional antihypertensive effect of magnesium supplementation with an angiotensin II receptor blocker in hypomagnesemic rats

Transient Receptor Potential Melastatin 7 Ion Channels Regulate Magnesium Homeostasis in Vascular Smooth Muscle Cells

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