Functional Upregulation of STIM-1/Orai-1-Mediated Store-Operated Ca2+ Contributing to the Hypertension Development Elicited by Chronic EtOH Consumption

Bomfim, Guilherme Henrique Souza; Méndez-López, Iago; Arranz-Tagarro, Juan Alberto; Carbonel, Adriana Aparecida Ferraz; Roman‐Campos, Danilo; Padín, Juan Fernando; Garcı́a, Antonio G.; Jurkiewicz, Aron; Jurkiewicz, Neide Hyppolito

doi:10.2174/1570161115666170201122750

Cited by 17 publications

(8 citation statements)

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“…were calculated by integrating the transients versus time during the stimulus duration for each experiment. The SOCE slope (increase or decrease) parameter was fitted by the GraphPad Prism software using the one-phase association equation [2]. Data represents the mean ± SEM of the minimum of three independent experiments.…”

Section: Data Analyses and Statisticsmentioning

confidence: 99%

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TRPM7 activation potentiates SOCE in enamel cells but requires ORAI

Bomfim

Costiniti

et al. 2020

Cell Calcium

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Calcium (Ca 2+) release-activated Ca 2+ (CRAC) channels mediated by STIM1/2 and ORAI (ORAI1-3) proteins form the dominant store-operated Ca 2+ entry (SOCE) pathway in a variety of cells. Among these, the enamel-forming cells known as ameloblasts rely on CRAC channel function to enable Ca 2+ influx, which is important for enamel mineralization. This key role of the CRAC channel is supported by human mutations and animal models lacking STIM1 and ORAI1, which results in enamel defects and hypomineralization. A number of recent reports have highlighted the role of the chanzyme TRPM7 (transient receptor potential melastanin 7), a transmembrane protein containing an ion channel permeable to divalent cations (Mg 2+ , Ca 2+), as a modulator of SOCE. This raises the question as to whether TRPM7 should be considered an alternative route for Ca 2+ influx, or if TRPM7 modifies CRAC channel activity in enamel cells. To address these questions, we monitored Ca 2+ influx mediated by SOCE using the pharmacological TRPM7 activator naltriben and the inhibitor NS8593 in rat primary enamel cells and in the murine ameloblast cell line LS8 cells stimulated with thapsigargin. We also measured Ca 2+ dynamics in ORAI1/2-deficient (shOrai1/2) LS8 cells and in cells with siRNA knock-down of Trpm7. We found that primary enamel cells stimulated with theTRPM7 activator potentiated Ca 2+ influx via SOCE compared to control cells. However, blockade of TRPM7 with NS8593 did not decrease the SOCE peak. Furthermore, activation of TRPM7 in shOrai1/2 LS8 cells lacking SOCE failed to elicit Ca 2+ influx, and Trpm7 knock-down had no effect on SOCE. Taken together, our data suggest that TRPM7 is a positive modulator of SOCE potentiating Ca 2+ influx in enamel cells, but its function is fully dependent on the prior activation of the ORAI channels.

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Section: Data Analyses and Statisticsmentioning

confidence: 99%

“…It is well established that calcium (Ca 2+ ) handling is one of the most widespread transducing systems, regulating a wide range of cell biology and pathophysiologic processes [1][2][3][4][5]. Enamel is the most calcified vertebrate tissue, requiring a steady supply of Ca 2+ for its mineralization.…”

Section: Introductionmentioning

confidence: 99%

TRPM7 activation potentiates SOCE in enamel cells but requires ORAI

Bomfim

Costiniti

et al. 2020

Cell Calcium

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“…Increased SOCE was detected in transient receptor potential 3 and 5 channels in monocytes of patients with essential hypertension [25]. Overexpression of STIM-1 resulted in hypertrophic arterial remodeling and cardiac hypertrophy in chronic ethanol-induced hypertensive rats [26]. For example, gastrodin, an agent used to treat hypertension, was found to suppress SOCE by reducing the expression of STIM-1 in a phenyl-ephrine-induced mouse model of cardiac hypertrophy [27].…”

Section: Discussionmentioning

confidence: 99%

Codonopsis lanceolata Contributes to Ca2+ Homeostasis by Mediating SOCE and PLC/IP3 Pathways in Vascular Endothelial and Smooth Muscle Cells

et al. 2020

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Codonopsis lanceolata has been widely used as an anti-inflammatory and anti-lipogenic agent in traditional medicine. Recently, C. lanceolata was reported to prevent hypertension by improving vascular function. This study evaluated the effects of C. lanceolata and its major component lancemaside A on cytosolic calcium concentration in vascular endothelial cells and vascular smooth muscle cells. Cytosolic calcium concentration was measured using fura-2 AM fluorescence. C. lanceolata or lancemaside A increased the cytosolic calcium concentration by releasing Ca2+ from the endoplasmic reticulum and sarcoplasmic reticulum and by Ca2+ entry into endothelial cells and vascular smooth muscle cells from extracellular sources. The C. lanceolata- and lancemaside A-induced cytosolic calcium concentration increases were significantly inhibited by lanthanum, an inhibitor of non-selective cation channels, in both endothelial cells and vascular smooth muscle cells. Moreover, C. lanceolata and lancemaside A significantly inhibited store-operated Ca2+ entry under pathological extracellular Ca2+ levels. In Ca2+-free extracellular fluid, increases in the cytosolic calcium concentration induced by C. lanceolata or lancemaside A were significantly inhibited by U73122, an inhibitor of phospholipase C, and 2-APB, an inositol 1,4,5-trisphosphate receptor antagonist. In addition, dantrolene treatment, which inhibits Ca2+ release through ryanodine receptor channels, also inhibited C. lanceolata- or lancemaside A-induced increases in the cytosolic calcium concentration through the phospholipase C/inositol 1,4,5-trisphosphate pathway. These results suggest that C. lanceolata and lancemaside A increase the cytosolic calcium concentration through the non-selective cation channels and phospholipase C/inositol 1,4,5-trisphosphate pathways under physiological conditions and inhibit store-operated Ca2+ entry under pathological conditions in endothelial cells and vascular smooth muscle cells. C. lanceolata or lancemaside A can protect endothelial cells and vascular smooth muscle cells by maintaining cytosolic calcium concentration homeostasis, suggesting possible applications for these materials in diets for preventing vascular damage.

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“…We found that A-769662 inhibited the steady-state contraction induced by CPA in FA in a manner similar to the selective store-operated Ca 2+ channel inhibitor, YM-58483 ( Harper and Poole, 2011 ). Notably, YM-58483 was shown to inhibit STIM-1/Orai-1 induced store-operated Ca 2+ entry in ethanol-treated rats ( Souza Bomfim et al, 2017 ). Thus, we propose that one mechanism by which A-769662 causes VSM relaxation is via inhibition of store-operated Ca 2+ entry.…”

Section: Discussionmentioning

confidence: 99%

The AMP-Dependent Protein Kinase (AMPK) Activator A-769662 Causes Arterial Relaxation by Reducing Cytosolic Free Calcium Independently of an Increase in AMPK Phosphorylation

et al. 2017

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Although recent studies reveal that activation of the metabolic and Ca2+ sensor AMPK strongly inhibits smooth muscle contraction, there is a paucity of information about the potential linkage between pharmacological AMPK activation and vascular smooth muscle (VSM) contraction regulation. Our aim was to test the general hypothesis that the allosteric AMPK activator A-769662 causes VSM relaxation via inhibition of contractile protein activation, and to specifically determine which activation mechanism(s) is(are) affected. The ability of A-769662 to cause endothelium-independent relaxation of contractions induced by several contractile stimuli was examined in large and small musculocutaneous and visceral rabbit arteries. For comparison, the structurally dissimilar AMPK activators MET, SIM, and BBR were assessed. A-769662 displayed artery- and agonist-dependent differential inhibitory activities that depended on artery size and location. A-769662 did not increase AMPK-pT172 levels, but did increase phosphorylation of the downstream AMPK substrate, acetyl-CoA carboxylase (ACC). A-769662 did not inhibit basal phosphorylation levels of several contractile protein regulatory proteins, and did not alter the activation state of rhoA. A-769662 did not inhibit Ca2+- and GTPγS-induced contractions in β-escin-permeabilized muscle, suggesting that A-769662 must act by inhibiting Ca2+ signaling. In intact artery, A-769662 immediately reduced basal intracellular free calcium ([Ca2+]i), inhibited a stimulus-induced increase in [Ca2+]i, and inhibited a cyclopiazonic acid (CPA)-induced contraction. MET increased AMPK-pT172, and caused neither inhibition of contraction nor inhibition of [Ca2+]i. Together, these data support the hypothesis that the differential inhibition of stimulus-induced arterial contractions by A-769662 was due to selective inhibition of a Ca2+ mobilization pathway, possibly involving CPA-dependent Ca2+ entry via an AMPK-independent pathway. That MET activated AMPK without causing arterial relaxation suggests that AMPK activation does not necessarily cause VSM relaxation.

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Functional Upregulation of STIM-1/Orai-1-Mediated Store-Operated Ca2+ Contributing to the Hypertension Development Elicited by Chronic EtOH Consumption

Abstract: These findings suggest that hypertrophic aortic remodeling and abnormal contraction triggered mainly by Ca2+ overload via STIM-1/Orai-1-mediated SOCE through SOCCs are involved hypertension developed by EtOH consumption.

Cited by 17 publications

References 0 publications

TRPM7 activation potentiates SOCE in enamel cells but requires ORAI

TRPM7 activation potentiates SOCE in enamel cells but requires ORAI

Codonopsis lanceolata Contributes to Ca2+ Homeostasis by Mediating SOCE and PLC/IP3 Pathways in Vascular Endothelial and Smooth Muscle Cells

The AMP-Dependent Protein Kinase (AMPK) Activator A-769662 Causes Arterial Relaxation by Reducing Cytosolic Free Calcium Independently of an Increase in AMPK Phosphorylation

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