Activation of the Na
 +
 -H
 +
 Exchanger Modulates Angiotensin II–Stimulated Na
 +
 -Dependent Mg
 2+
 Transport in Vascular Smooth Muscle Cells in Genetic Hypertension

Touyz, Rhian M.; Schiffrin, Ernesto L.

doi:10.1161/01.hyp.34.3.442

Cited by 39 publications

(22 citation statements)

References 57 publications

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“…104-111 Also, in Ang II-induced hypertension in rats, inhibition of the Na + /Mg 2+ antiport resulted in reduced blood pressure, normalization of vascular and renal MAP kinase activity and improved vascular structure. [104][105][106][107][108][109][110][111] TRPM6 and TRPM7 have been implicated in a number of vascular pathologies, including endothelial dysfunction and hypertension. 112, 113 We and others demonstrated that VSMC from mouse, rat and human resistance arteries possess TRPM6 and TRPM7 cation channels and that TRPM7 is critically involved in regulating Mg 2+ influx, cell viability, proliferation and contraction/dilation.…”

Section: Trpm7 Mg 2+ and Hypertensionmentioning

confidence: 99%

Transient Receptor Potential Melastatin 7 (TRPM7) Cation Channels, Magnesium and the Vascular System in Hypertension

Yogi

Callera

Antunes

et al. 2011

Circ J

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Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp ypertension is the most common chronic disease in developed and developing societies and a major risk factor for morbidity and mortality. 1, 2 The most common form of hypertension is 'essential hypertension' the causes of which remain unknown. Among the many factors implicated in the pathophysiology of hypertension are neurohumoral, renal, metabolic, race, genetic, environmental factors and alterations in cellular cations, such as sodium (Na + ), calcium (Ca 2+ ), potassium (K + ) and magnesium (Mg 2+ ) have been shown to be related to the increase in systolic blood pressure. 3-7Mg 2+ , an abundant intracellular divalent cation, functions as an allosteric modulator of several proteins, controls nucleotide and protein synthesis, regulates Na + , K + , and Ca 2+ channels and is critical for myriad enzymatic reactions, particularly those involving kinases. 8,9 Mg 2+ is stored primarily in bone and the intracellular compartments of muscle and soft tissues, with less than 1% of total body Mg 2+ circulating in the blood. 9,10 Mg 2+ homeostasis depends primarily on the balance between intestinal uptake and renal excretion. Mg 2+ deficiency results from reduced dietary intake, intestinal malabsorption or renal loss. Mammalian cells tightly control magnesium levels within a narrow range (0.70-1.1 mmol/L) by specific regulatory mechanisms operating at the level of intraorganelle compartmentalization, intracellular magnesium buffering and at regulating magnesium entry and efflux across the cell membrane.Epidemiological studies indicate that low Mg 2+ status is associated with many diseases including diabetes, metabolic syndrome, dyslipidemia and hypertension.

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Section: Trpm7 Mg 2+ and Hypertensionmentioning

confidence: 99%

Transient Receptor Potential Melastatin 7 (TRPM7) Cation Channels, Magnesium and the Vascular System in Hypertension

Yogi

Callera

Antunes

et al. 2011

Circ J

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“…16,17 We reported that Mg 2ϩ efflux is regulated by a Na ϩ -dependent Mg 2ϩ exchanger linked to the Na ϩ /H ϩ antiporter in VSMCs. 15,18 Although studies of Mg 2ϩ fluxes in mammalian cells have indicated the presence of functionally active plasma membrane Mg 2ϩ transport mechanisms, proteins responsible for these fluxes have not been identified. 19 Recent investigations suggested that two novel ion channels of the long, or melastatin-related, transient receptor potential (TRPM) ion channel subfamily, TRPM6 and TRPM7, are critically involved in Mg 2ϩ influx in epithelial and neuronal cells.…”

mentioning

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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“…Studies with perfused heart and liver, as well as with cardiac myocytes and hepatocytes, have demonstrated that Mg 2ϩ fluxes are under the control of various hormones, such as insulin, endothelin-1, norepinephrine, epinephrine, aldosterone, and arginine vasopressin (22)(23)(24)(25)(26)(27). We recently reported that angiotensin II (Ang II), 1 a potent vasoactive agent, modulates [Mg 2ϩ ] i in vascular smooth muscle cells and in platelets (17,28,29 …”

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confidence: 99%

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

Touyz

Mercure

Reudelhuber

2001

Journal of Biological Chemistry

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Activation of the Na ⁺ -H ⁺ Exchanger Modulates Angiotensin II–Stimulated Na ⁺ -Dependent Mg ²⁺ Transport in Vascular Smooth Muscle Cells in Genetic Hypertension

Abstract: Abstract-This

Cited by 39 publications

References 57 publications

Transient Receptor Potential Melastatin 7 (TRPM7) Cation Channels, Magnesium and the Vascular System in Hypertension

Transient Receptor Potential Melastatin 7 (TRPM7) Cation Channels, Magnesium and the Vascular System in Hypertension

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

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

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Activation of the Na + -H + Exchanger Modulates Angiotensin II–Stimulated Na + -Dependent Mg 2+ Transport in Vascular Smooth Muscle Cells in Genetic Hypertension

Abstract: Abstract-This

Cited by 39 publications

References 57 publications

Transient Receptor Potential Melastatin 7 (TRPM7) Cation Channels, Magnesium and the Vascular System in Hypertension

Transient Receptor Potential Melastatin 7 (TRPM7) Cation Channels, Magnesium and the Vascular System in Hypertension

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

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

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Activation of the Na ⁺ -H ⁺ Exchanger Modulates Angiotensin II–Stimulated Na ⁺ -Dependent Mg ²⁺ Transport in Vascular Smooth Muscle Cells in Genetic Hypertension