Na+–Ca2+ exchanger contributes to Ca2+extrusion in ATP-stimulated endothelium of intact rat aorta

Berra‐Romani, Roberto; Raqeeb, Abdul; Guzmán-Silva, Alejandro; Torres-Jácome, Julián; Tanzi, Franco; Moccia, Francesco

doi:10.1016/j.bbrc.2010.03.153

Cited by 16 publications

(24 citation statements)

References 31 publications

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“…We first probed MβCD (10 mM) efficacy in impairing caveolae-dependent signalling by testing its effect on SOCE. As shown elsewhere [27,35], SOCE sustains the Ca 2+ response to high concentrations of ATP (300 μM) in the endothelium of excised rat aorta. As shown in Figure 7A, MβCD significantly reduced the amplitudes of both the initial Ca 2+ peak and the subsequent plateau, which are both supported by SOCE [27].…”

Section: Resultssupporting

confidence: 59%

Ca2+-dependent nitric oxide release in the injured endothelium of excised rat aorta: a promising mechanism applying in vascular prosthetic devices in aging patients

et al. 2013

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BackgroundNitric oxide is key to endothelial regeneration, but it is still unknown whether endothelial cell (EC) loss results in an increase in NO levels at the wound edge. We have already shown that endothelial damage induces a long-lasting Ca2+ entry into surviving cells though connexin hemichannels (CxHcs) uncoupled from their counterparts on ruptured cells. The physiological outcome of injury-induced Ca2+ inflow is, however, unknown.MethodsIn this study, we sought to determine whether and how endothelial scraping induces NO production (NOP) in the endothelium of excised rat aorta by exploiting the NO-sensitive fluorochrome, DAF-FM diacetate and the Ca2+-sensitive fluorescent dye, Fura-2/AM.ResultsWe demonstrated that injury-induced NOP at the lesion site is prevented in presence of the endothelial NO synthase inhibitor, L-NAME, and in absence of extracellular Ca2+. Unlike ATP-dependent NO liberation, the NO response to injury is insensitive to BTP-2, which selectively blocks store-operated Ca2+ inflow. However, injury-induced NOP is significantly reduced by classic gap junction blockers, and by connexin mimetic peptides specifically targeting Cx37Hcs, Cx40HCs, and Cx43Hcs. Moreover, disruption of caveolar integrity prevents injury-elicited NO signaling, but not the accompanying Ca2+ response.ConclusionsThe data presented provide the first evidence that endothelial scraping stimulates NO synthesis at the wound edge, which might both exert an immediate anti-thrombotic and anti-inflammatory action and promote the subsequent re-endothelialization.

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Section: Resultssupporting

confidence: 59%

Ca2+-dependent nitric oxide release in the injured endothelium of excised rat aorta: a promising mechanism applying in vascular prosthetic devices in aging patients

et al. 2013

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“…Notably, NCX-mediated Ca 2+ inflow has recently been reported in the intact endothelium of excised rat aorta challenged with acetylcholine [20]. In a first set of experiments, we found that blocking NCX activity by replacing extracellular Na + with an equimolar amount of N-methyl- D -glucamine [21], or KB-R 7943 (8 µ M ) (a selective blocker of the reverse mode) [20,22], did not affect the prolonged decay phase (fig. 5A, B).…”

Section: Resultsmentioning

confidence: 99%

The Mechanism of Injury-Induced Intracellular Calcium Concentration Oscillations in the Endothelium of Excised Rat Aorta

Berra‐Romani¹,

Raqeeb

Torres-Jácome

et al. 2011

J Vasc Res

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Endothelial injury is the primary event that leads to a variety of severe vascular disorders. Mechanical injury elicits a Ca²⁺ response in the endothelium of excised rat aorta, which comprises an initial Ca²⁺ release from inositol-1,4,5-trisphosphate (InsP₃)-sensitive stores followed by a long-lasting decay phase due to Ca²⁺ entry through uncoupled connexons. The Ca²⁺ signal may also adopt an oscillatory pattern, the molecular underpinnings of which are unclear. In the light of the role played by Ca²⁺ spiking in tissue regeneration, this study aimed to unveil the mechanisms underlying injury-induced Ca²⁺ oscillations. The latter reversibly ceased upon removal of extracellular Ca²⁺ or addition of the gap junction blockers heptanol, 18 α,β-glycyrrhetinic acid, La³⁺ and Ni²⁺, but were insensitive to BTP-2 and SKF 96365. The spiking response was abolished by inhibiting the Ca²⁺ entry mode of the Na⁺/Ca²⁺ exchanger (NCX). The InsP₃-producing agonist ATP resumed Ca²⁺ oscillations in silent cells, while the phospholipase C inhibitor U73122 suppressed them. Injury-induced Ca²⁺ transients were prevented by the sarcoplasmic-endoplasmic reticulum calcium ATPase (SERCA) blockers thapsigargin and cyclopiazonic acid, while they were unaffected by suramin and genistein. These data show for the first time that the coordinated interplay between NCX-mediated Ca²⁺ entry and InsP₃-dependent Ca²⁺ release contributes to injury-induced intracellular Ca²⁺ concentration oscillations.

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“…CCE was not affected by AGEs and, when AGEs were added to the cells following ATP, or when IP 3 receptors were blocked, extracellular Ca 2+ entry was enhanced, suggesting the glycated proteins may have an action to induce Ca 2+ entry or enhance CCE into the BAEC. It should be noted that, unlike thapsigargin and ionomycin, ATP-induced influx of extracellular Ca 2+ into vascular endothelial cells probably occurs by mechanisms additional to CCE, mostly likely receptor-operated channels such as TRPC1, 3, and 4 (Kamouchi et al, 1999; Brough et al, 2001; Freichel et al, 2001; Sandow et al, 2012), along with other possible channels (Kwan et al, 2009) and membrane Ca 2+ -exchangers such as Na + -Ca 2+ (Berra-Romani et al, 2010). The mechanism of CCE into vascular endothelial cells is not fully understood and somewhat controversial (Beech, 2009) with various TRP channels identified as being involved in the process (Cioffi et al, 2005; Antoniotti et al, 2006; Senadheera et al, 2012; Sonkusare et al, 2012) along with the proteins crucial for I CRAC , Stim1, and Orai1 (Abdullaev et al, 2008; Hirano et al, 2009; Antigny et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Advanced Glycation End Products Acutely Impair Ca2+ Signaling in Bovine Aortic Endothelial Cells

Naser¹,

Januszewski²,

Brown³

et al. 2013

Front. Physiol.

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Post-translational modification of proteins in diabetes, including formation of advanced glycation end products (AGEs) are believed to contribute to vascular dysfunction and disease. Impaired function of the endothelium is an early indicator of vascular dysfunction in diabetes and as many endothelial cell processes are dependent upon intracellular [Ca2+] and Ca2+ signaling, the aim of this study was to examine the acute effects of AGEs on Ca2+ signaling in bovine aortic endothelial cells (BAEC). Ca2+ signaling was studied using the fluorescent indicator dye Fura-2-AM. AGEs were generated by incubating bovine serum albumin with 0–250 mM glucose or glucose-6-phosphate for 0–120 days at 37°C. Under all conditions, the main AGE species generated was carboxymethyl lysine (CML) as assayed using both gas-liquid chromatograph-mass spectroscopy and high-performance liquid chromatography. In Ca2+-replete solution, exposure of BAEC to AGEs for 5 min caused an elevation in basal [Ca2+] and attenuated the increase in intracellular [Ca2+] caused by ATP (100 μM). In the absence of extracellular Ca2+, exposure of BAEC to AGEs for 5 min caused an elevation in basal [Ca2+] and attenuated subsequent intracellular Ca2+ release caused by ATP, thapsigargin (0.1 μM), and ionomycin (3 μM), but AGEs did not affect extracellular Ca2+ entry induced by the re-addition of Ca2+ to the bathing solution in the presence of any of these agents. The anti-oxidant α-lipoic acid (2 μM) and NAD(P)H oxidase inhibitors apocynin (500 μM) and diphenyleneiodonium (1 μM) abolished these effects of AGEs on BAECs, as did the IP3 receptor antagonist xestospongin C (1 μM). In summary, AGEs caused an acute depletion of Ca2+ from the intracellular store in BAECs, such that the Ca2+ signal stimulated by the subsequent application other agents acting upon this store is reduced. The mechanism may involve generation of reactive oxygen species from NAD(P)H oxidase and possible activation of the IP3 receptor.

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Na+–Ca2+ exchanger contributes to Ca2+extrusion in ATP-stimulated endothelium of intact rat aorta

Cited by 16 publications

References 31 publications

Ca2+-dependent nitric oxide release in the injured endothelium of excised rat aorta: a promising mechanism applying in vascular prosthetic devices in aging patients

Ca2+-dependent nitric oxide release in the injured endothelium of excised rat aorta: a promising mechanism applying in vascular prosthetic devices in aging patients

The Mechanism of Injury-Induced Intracellular Calcium Concentration Oscillations in the Endothelium of Excised Rat Aorta

Advanced Glycation End Products Acutely Impair Ca2+ Signaling in Bovine Aortic Endothelial Cells

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