Plasma membrane calcium ATPase proteins as novel regulators of signal transduction pathways

Holton, Mary Louisa; Wang, Weiguang; Emerson, Michael; Neyses, Ludwig; Armesilla, Ángel Luis

doi:10.4331/wjbc.v1.i6.201

Cited by 42 publications

(33 citation statements)

References 60 publications

(95 reference statements)

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“…De este modo, se ha observado interacción funcional de las ATP2Bs con proteínas dependientes de la calmodulina como las sintasas de óxido nítrico endotelial, (eNOS) y neuronal (nNOS), y la cinasa de serina dependiente de calcio (CASK), entre otras (43,44,94,95). Por lo anterior, es posible que esta enzima se encuentre también modulando la función de las aduccinas, ya que estas proteínas dependen de la acción de la calmodulina (39).…”

Section: Discussionunclassified

“…Los principales sistemas fisiológicos que se encuentran involucrados en el control de la presión arterial son el sistema renina-angiotensina-aldosterona, el endotelio vascular, la transducción de señales por vía del sistema nervioso y las proteínas del citoesqueleto, que se encargan del mantenimiento del flujo sanguíneo (presión sanguínea y volumen de fluidos extracelulares en el cuerpo), mediación de reacciones de vasodilatación-vasoconstricción y la regulación de la concentración de sales (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44).…”

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Asociación y efectos de interacción en los genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2 sobre la hipertensión en población antioqueña

et al. 2013

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Section: Discussionunclassified

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Asociación y efectos de interacción en los genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2 sobre la hipertensión en población antioqueña

et al. 2013

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“…It is well documented that calcium (Ca 2+ ) is involved in signal transduction in excitable and non-excitable cells acting in both extracellular and intracellular compartments [4,8,16]. Magnesium (Mg 2+ ) is a cofactor in more than 300 enzymatic reactions and is required for muscle contraction, glucose utilization, and synthesis of nucleic acids, fat and proteins [19].…”

Section: Introductionmentioning

confidence: 99%

Calcium, magnesium and phosphorus dietary intake in active and sedentary Polish students

Malara

Tkaczyk

Kęska

et al. 2017

Biomedical Human Kinetics

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SummaryStudy aim: To evaluate energy, macronutrient, calcium, magnesium, and phosphate daily intake in young healthy Polish male students. Material and methods: Two hundred and sixteen participants were physical education students engaged in regular physical activity (about 9 h/week) and were recognized as physically active. One hundred and fourteen students were from other specializations participating in 1.5 h/week gymnastics classes and were recognized as sedentary. Body mass and height were measured using standard medical equipment. Body fat was evaluated from four skinfold measurements. In all subjects daily intake of energy, protein, fat, carbohydrates, calcium, magnesium and phosphate was briefly assessed from 24-hour food records taken over 4 days. Results: The active students' diet was characterized by significantly higher energy, macronutrient and mineral daily intake. Moreover, calcium to phosphorus and calcium to magnesium ratios in active subjects were higher than in sedentary ones. There was no significant difference between groups in protein or magnesium intake expressed per 1000 kcal. In contrast, daily intake of fat and phosphate expressed per 1000 kcal was significantly lower in the active students vs. sedentary ones (p < 0.001 and p < 0.05 for fat and phosphate, respectively). Active students were characterized by significantly higher carbohydrate and calcium intake per 1000 kcal in comparison with their sedentary counterparts (p < 0.001 for both variables). Conclusions:The dietary pattern of active students was found to be slightly but significantly better than that of their sedentary counterparts. However, in both groups it was far from being a healthy one.

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“…PMCA4 is thought to downregulate calcineurin/NFAT pathway activity through a molecular interaction that sequesters calcineurin into low calcium micro-domains created by the pump's calcium extrusion activity [18]. Supporting this idea, disruption of the PMCA4/calcineurin interaction notably potentiates calcineurin/NFAT signalling [4].…”

Section: Ata Enhances Vegf-induced Calcineurin Signalling In Endothelmentioning

confidence: 99%

Selective inhibition of plasma membrane calcium ATPase 4 improves angiogenesis and vascular reperfusion

Kurusamy

López-Maderuelo

Little

et al. 2017

Journal of Molecular and Cellular Cardiology

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Aims: Ischaemic cardiovascular disease is a major cause of morbidity and mortality worldwide. Despite promising results from pre-clinical animal models, VEGF-based strategies for therapeutic angiogenesis have yet to achieve successful reperfusion of ischaemic tissues in patients. Failure to restore efficient VEGF activity in the ischaemic organ remains a major problem in current pro-angiogenic therapeutic approaches. Plasma membrane calcium ATPase 4 (PMCA4) negatively regulates VEGF-activated angiogenesis via inhibition of the calcineurin/NFAT signalling pathway. PMCA4 activity is inhibited by the small molecule aurintricarboxylic acid (ATA). We hypothesize that inhibition of PMCA4 with ATA might enhance VEGF-induced angiogenesis. Methods and results: We show that inhibition of PMCA4 with ATA in endothelial cells triggers a marked increase in VEGF-activated calcineurin/NFAT signalling that translates into a strong increase in endothelial cell motility and blood vessel formation. ATA enhances VEGF-induced calcineurin signalling by disrupting the interaction between PMCA4 and calcineurin at the endothelial-cell membrane. ATA concentrations at the nanomolar range, that efficiently inhibit PMCA4, had no deleterious effect on endothelial-cell viability or zebrafish embryonic development. However, high ATA concentrations at the micromolar level impaired endothelial cell viability and tubular morphogenesis, and were associated with toxicity in zebrafish embryos. In mice undergoing experimentally-induced hindlimb ischaemia, ATA treatment significantly increased the reperfusion of post-ischaemic limbs. Conclusions: Our study provides evidence for the therapeutic potential of targeting PMCA4 to improve VEGFbased pro-angiogenic interventions. This goal will require the development of refined, highly selective versions of ATA, or the identification of novel PMCA4 inhibitors.

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Plasma membrane calcium ATPase proteins as novel regulators of signal transduction pathways

Cited by 42 publications

References 60 publications

Asociación y efectos de interacción en los genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2 sobre la hipertensión en población antioqueña

Asociación y efectos de interacción en los genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2 sobre la hipertensión en población antioqueña

Calcium, magnesium and phosphorus dietary intake in active and sedentary Polish students

Selective inhibition of plasma membrane calcium ATPase 4 improves angiogenesis and vascular reperfusion

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