Endothelial calcium dynamics, connexin channels and blood–brain barrier function

Bock, Marijke De; Wang, Nan; Decrock, Elke; Bol, Mélissa; Gadicherla, Ashish K.; Culot, Maxime; Cecchelli, Roméo; Bultynck, Geert; Leybaert, Luc

doi:10.1016/j.pneurobio.2013.06.001

Cited by 151 publications

(128 citation statements)

References 296 publications

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“…Mitochondrial dysfunction results in deficient ATP production, which impairs ATP-dependent transport mechanisms in the plasma and ER membranes, such as the sodium (Na + /K + -ATPase) and calcium (Ca 2+ -ATPase) pumps [9,203], and the ABC transporters [9]. Impaired Na + and K + homeostasis in the perivascular space influences cell membrane depolarization in neurons, affecting neuronal and synaptic functions [9].…”

Section: Consequences Of Deficient Atp Productionmentioning

confidence: 99%

“…This in turn affects endothelial NO synthase (eNOS) activity [204] and BBB permeability [203]. The deficient ATP production of dysfunctional mitochondria also leads to the dysregulation of ABC transporters, affecting brain supply of glucose and other nutrients, as well as A clearance from the perivascular space [9].…”

Section: Consequences Of Deficient Atp Productionmentioning

confidence: 99%

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Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Marco

Venneri

Farkas

et al. 2015

Neurobiology of Disease

232

185

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Article available under the terms of the CC-BY-NC-ND licence (https://creativecommons.org/licenses/by-nc-nd/4.0/) eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request.

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Section: Consequences Of Deficient Atp Productionmentioning

confidence: 99%

Section: Consequences Of Deficient Atp Productionmentioning

confidence: 99%

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Marco

Venneri

Farkas

et al. 2015

Neurobiology of Disease

232

185

View full text Add to dashboard Cite

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“…14 In blood-brain barrier endothelial cells, inhibiting hemichannels or ATP signalling blocked bradykinin-triggered Ca 2þ oscillations and prevented vascular barrier dysfunction. 15,16 Vascular cells express several Cxs, including Cx37, Cx40, and Cx43 in endothelial cells, and Cx37, Cx43, and Cx45 in SMCs. [17][18][19] Pannexins are related to the Cx-protein family: they have a similar topology but no sequence homology with Cxs and form plasma membrane channels that, like Cx-hemichannels, are Ca 2þ -permeable and function as ATP release channels.…”

Section: Introductionmentioning

confidence: 99%

At the cross-point of connexins, calcium, and ATP: blocking hemichannels inhibits vasoconstriction of rat small mesenteric arteries

et al. 2016

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“…Nonetheless, endothelial mitochondria rapidly sequester cytosolic Ca 2ϩ transients to influence vascular function (12). Repetitive Ca 2ϩ oscillations are commonly observed in ECs (13)(14)(15) and influence NF-B transcriptional activity (16) and expression of vascular adhesion molecules and interleukins (17,18). Whether Ca 2ϩ -mediated alterations in mitochondrial bioenergetics can influence Ca 2ϩ -regulated cytosolic signaling cascades is unclear.…”

mentioning

confidence: 99%

Mitochondrial Matrix Ca²⁺ Accumulation Regulates Cytosolic NAD⁺/NADH Metabolism, Protein Acetylation, and Sirtuin Expression

Marcu

Wiczer

Neeley

et al. 2014

Molecular and Cellular Biology

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Mitochondrial calcium uptake stimulates bioenergetics and drives energy production in metabolic tissue. It is unknown how a calcium-mediated acceleration in matrix bioenergetics would influence cellular metabolism in glycolytic cells that do not require mitochondria for ATP production. Using primary human endothelial cells (ECs), we discovered that repetitive cytosolic calcium signals (oscillations) chronically loaded into the mitochondrial matrix. Mitochondrial calcium loading in turn stimulated bioenergetics and a persistent elevation in NADH. Rather than serving as an impetus for mitochondrial ATP generation, matrix NADH rapidly transmitted to the cytosol to influence the activity and expression of cytosolic sirtuins, resulting in global changes in protein acetylation. In endothelial cells, the mitochondrion-driven reduction in both the cytosolic and mitochondrial NAD ؉ / NADH ratio stimulated a compensatory increase in SIRT1 protein levels that had an anti-inflammatory effect. Our studies reveal the physiologic importance of mitochondrial bioenergetics in the metabolic regulation of sirtuins and cytosolic signaling cascades.

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Endothelial calcium dynamics, connexin channels and blood–brain barrier function

Cited by 151 publications

References 296 publications

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

At the cross-point of connexins, calcium, and ATP: blocking hemichannels inhibits vasoconstriction of rat small mesenteric arteries

Mitochondrial Matrix Ca²⁺ Accumulation Regulates Cytosolic NAD⁺/NADH Metabolism, Protein Acetylation, and Sirtuin Expression

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Endothelial calcium dynamics, connexin channels and blood–brain barrier function

Cited by 151 publications

References 296 publications

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

At the cross-point of connexins, calcium, and ATP: blocking hemichannels inhibits vasoconstriction of rat small mesenteric arteries

Mitochondrial Matrix Ca2+ Accumulation Regulates Cytosolic NAD+/NADH Metabolism, Protein Acetylation, and Sirtuin Expression

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Mitochondrial Matrix Ca²⁺ Accumulation Regulates Cytosolic NAD⁺/NADH Metabolism, Protein Acetylation, and Sirtuin Expression