Orai3 Surface Accumulation and Calcium Entry Evoked by Vascular Endothelial Growth Factor

Li, Jing; Bruns, Alexander-Francisco; Hou, Bing; Rode, Baptiste; Webster, Peter J.; Bailey, Marc A.; Appleby, Hollie L.; Moss, Nicholas K.; Ritchie, Judith; Yuldasheva, Nadira; Tumova, Sarka; Quinney, Matthew; McKeown, Lynn; Taylor, Hilary; Prasad, K. Raj; Burke, Dermot; O’Regan, David; Porter, Karen E.; Foster, Richard; Kearney, Mark T.; Beech, David J.

doi:10.1161/atvbaha.115.305969

Cited by 28 publications

(24 citation statements)

References 42 publications

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“…Similar to other endothelial cells types [ 108 , 109 ], SOCE is constitutively activated to refill the InsP 3 -dependent ER Ca 2+ pool and maintains basal Ca 2+ levels in mouse brain microvascular endothelial cells [ 76 ]. AA may induce extracellular Ca 2+ entry in vascular endothelial cells by prompting Orai1 to interact with Orai3 independently on Stim1 [ 110 ]. Nevertheless, Orai3 is not expressed in bEND5 cells, and therefore, this mechanism is unlikely to work in NVC [ 76 ].…”

Section: The Role Of Endothelial Ca 2+ Signalinmentioning

confidence: 99%

The Role of Endothelial Ca2+ Signaling in Neurovascular Coupling: A View from the Lumen

Guerra

Lucariello

Perna

et al. 2018

IJMS

104

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Background: Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity (NA) leads to local elevation in cerebral blood flow (CBF) to match the metabolic requirements of firing neurons. Following synaptic activity, an increase in neuronal and/or astrocyte Ca2+ concentration leads to the synthesis of multiple vasoactive messengers. Curiously, the role of endothelial Ca2+ signaling in NVC has been rather neglected, although endothelial cells are known to control the vascular tone in a Ca2+-dependent manner throughout peripheral vasculature. Methods: We analyzed the literature in search of the most recent updates on the potential role of endothelial Ca2+ signaling in NVC. Results: We found that several neurotransmitters (i.e., glutamate and acetylcholine) and neuromodulators (e.g., ATP) can induce dilation of cerebral vessels by inducing an increase in endothelial Ca2+ concentration. This, in turn, results in nitric oxide or prostaglandin E2 release or activate intermediate and small-conductance Ca2+-activated K+ channels, which are responsible for endothelial-dependent hyperpolarization (EDH). In addition, brain endothelial cells express multiple transient receptor potential (TRP) channels (i.e., TRPC3, TRPV3, TRPV4, TRPA1), which induce vasodilation by activating EDH. Conclusions: It is possible to conclude that endothelial Ca2+ signaling is an emerging pathway in the control of NVC.

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Section: The Role Of Endothelial Ca 2+ Signalinmentioning

confidence: 99%

The Role of Endothelial Ca2+ Signaling in Neurovascular Coupling: A View from the Lumen

Guerra

Lucariello

Perna

et al. 2018

IJMS

104

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“…These discrepancies could reflect the well known heterogeneity in terms of Ca 2+ signalling between hECFCs and mature endothelium [74]. However, AA has recently been shown to induce a robust Ca 2+ release in human umbilical vein ECs (HUVECs) when applied at >10 M [26].…”

Section: Arachidonic Acid Utilizes Intracellular Ca 2+ and No Signalsmentioning

confidence: 99%

“…The Ca 2+ response to AA in other cellular models is more complex and involves additional pathways, including: inositol-1,4,5-trisphosphate (InsP 3 ) receptors (InsP 3 Rs) and ryanodine receptors (RyRs) [20][21][22][23], that release Ca 2+ from the endoplasmic reticulum (ER), the most abundant endogenous Ca 2+ reservoir; the acidic Ca 2+ stores of the endolysosomal (EL) system [22]; AA-regulated Ca 2+ (ARC) channels and leukotriene C4 (LTC4)regulated Ca 2+ (LRC) channels, that are contributed from heteromers of the novel Ca 2+ -permeable channels Orai1 and Orai3 and are gated, respectively, by AA itself and its LOX-dependent metabolite LTC4 [24,25]. A recent study showed that Orai3 may mediate AA-and LTC4-dependent Ca 2+ inflow also in human vascular ECs [26], albeit it is not constitutively expressed on the plasma membrane.…”

Section: Introductionmentioning

confidence: 99%

Arachidonic acid-evoked Ca2+ signals promote nitric oxide release and proliferation in human endothelial colony forming cells

Zuccolo

Dragoni

Poletto

et al. 2016

Vascular Pharmacology

103

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Arachidonic acid (AA) stimulates endothelial cell (EC) proliferation through an increase in intracellular Ca concentration ([Ca]), that, in turn, promotes nitric oxide (NO) release. AA-evoked Ca signals are mainly mediated by Transient Receptor Potential Vanilloid 4 (TRPV4) channels. Circulating endothelial colony forming cells (ECFCs) represent the only established precursors of ECs. In the present study, we, therefore, sought to elucidate whether AA promotes human ECFC (hECFC) proliferation through an increase in [Ca] and the following activation of the endothelial NO synthase (eNOS). AA induced a dose-dependent [Ca] raise that was mimicked by its non-metabolizable analogue eicosatetraynoic acid. AA-evoked Ca signals required both intracellular Ca release and external Ca inflow. AA-induced Ca release was mediated by inositol-1,4,5-trisphosphate receptors from the endoplasmic reticulum and by two pore channel 1 from the acidic stores of the endolysosomal system. AA-evoked Ca entry was, in turn, mediated by TRPV4, while it did not involve store-operated Ca entry. Moreover, AA caused an increase in NO levels which was blocked by preventing the concomitant increase in [Ca] and by inhibiting eNOS activity with NG-nitro-l-arginine methyl ester (l-NAME). Finally, AA per se did not stimulate hECFC growth, but potentiated growth factors-induced hECFC proliferation in a Ca- and NO-dependent manner. Therefore, AA-evoked Ca signals emerge as an additional target to prevent cancer vascularisation, which may be sustained by ECFC recruitment.

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“…Although the mechanism was not thoroughly analyzed, they propose a Ca 2ϩ release-dependent mechanism for activation of this ORAI3 system in which VEGF-mediated Ca 2ϩ release activates cPLA2␣ to catalyze the production of AA, which in turn activates ORAI3 by exposing it to the surface membrane (55). Further studies will be needed to better understand the reciprocal regulation between the "classical" ORAI1-STIM1 SOCE activation and ORAI3 as previously shown for prostate cancer cells (23).…”

Section: Inducing Angiogenesismentioning

confidence: 95%

“…Besides ORAI1-STIM1, a study from the Beech group recently suggested a role for ORAI3 in VEGF-induced EC remodeling with a consequent role for in vitro and in vivo tubulogenesis (55). Although the mechanism was not thoroughly analyzed, they propose a Ca 2ϩ release-dependent mechanism for activation of this ORAI3 system in which VEGF-mediated Ca 2ϩ release activates cPLA2␣ to catalyze the production of AA, which in turn activates ORAI3 by exposing it to the surface membrane (55).…”

Section: Inducing Angiogenesismentioning

confidence: 99%

STIM and ORAI proteins: crucial roles in hallmarks of cancer

Fiorio

Kondratska

Prevarskaya

2016

American Journal of Physiology-Cell Physiology

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Intracellular Ca2+ signals play a central role in several cellular processes; therefore it is not surprising that altered Ca2+ homeostasis regulatory mechanisms lead to a variety of severe pathologies, including cancer. Stromal interaction molecules (STIM) and ORAI proteins have been identified as critical components of Ca2+ entry in both store-dependent (SOCE mechanism) and independent by intracellular store depletion and have been implicated in several cellular functions. In recent years, both STIMs and ORAIs have emerged as possible molecular targets for cancer therapeutics. In this review we focus on the role of STIM and ORAI proteins in cancer progression. In particular we analyze their role in the different hallmarks of cancer, which represent the organizing principle that describes the complex multistep process of neoplastic diseases.

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Orai3 Surface Accumulation and Calcium Entry Evoked by Vascular Endothelial Growth Factor

Abstract: Supplemental Digital Content is available in the text.

Cited by 28 publications

References 42 publications

The Role of Endothelial Ca2+ Signaling in Neurovascular Coupling: A View from the Lumen

The Role of Endothelial Ca2+ Signaling in Neurovascular Coupling: A View from the Lumen

Arachidonic acid-evoked Ca2+ signals promote nitric oxide release and proliferation in human endothelial colony forming cells

STIM and ORAI proteins: crucial roles in hallmarks of cancer

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