Functional impairment of endothelial cells by the antimycotic amphotericin B

Pelzmann, Brigitte; Giuro, Cristiana Maria Loredana Di; Zorn-Pauly, Klaus; Rossmann, Christine; Hallström, Seth; Fameli, Nicola

doi:10.1016/j.bbrc.2016.02.054

Cited by 3 publications

(4 citation statements)

References 34 publications

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“…Infigure 7we plotted E NCX = 3 E Na − 2 E Ca , where E Na and E Ca are the Nernst potentials for Na + and Ca 2+ , respectively, as a function of [Ca 2+ ] i at 3 different possible values of [Na + ] i . Two values of the membrane potential of our cells are also plotted: V m ≈ −2 mV (blue line) is the one we expect in depolarized conditions (as determined in[28]), while V m ≈ −50 mV (green line) is the one calculated by Goldman's equation, using permeability values found in the literature[41]. (Other reported V m measurements in EC in the literature under physiological conditions indicate values virtually always around, or less negative than, −40 mV[33,34,[42][43][44][45][46].…”

supporting

confidence: 56%

“…Moreover, depolarizing the membrane essentially clamps its potential at a value around 0 mV [28], which holds fixed the driving force of the NCX, given by the relationship E NCX < V m between the NCX reversal potential, E NCX , and the membrane potential, V m . This is important since the V m of EC (EA.hy926 included) has been shown to be rather variable [28,33,34] and this variability will also reflect in the driving force of the NCX. Under these experimental conditions, we recorded a greatly diminished global [Ca 2+ ] i signal during the nCa 2+ phase, while the ER is refilled to the same level observed in polarized cells (solid blue circles in figure 2C and D).…”

Section: Er Ca 2+ Is Refilled By Extracellular Ca 2+ Regardless Of Mementioning

confidence: 99%

“…Due to the reported variability of the EC's membrane potential, V m , (see [28] and references therein) and the necessity to operate with a stable driving force of the NCX, we opted to work under conditions of membrane depolarization by using a superfusing solution with 70 mM [K + ] (with ≈ 70 mM [Na + ] for osmotic balance). This "driving force clamp" method has been employed before [29] and in our experiments also serves the purpose of highlighting the NCX-mediated Ca 2+ influx in relation to that of TRPC and Orai1.…”

Section: Introductionmentioning

confidence: 99%

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Na⁺/Ca²⁺exchangers and Orai channels jointly refill endoplasmic reticulum (ER) Ca²⁺via ER nanojunctions in vascular endothelial cells

Giuro

Shrestha

Malli

et al. 2016

Preprint

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We investigated the role of Na + /Ca 2+ exchange (NCX) in the refilling of endoplasmic reticulum by about 20%, thereby supporting the hypothesis that this process of privileged ER refilling is junction-mediated. Junctions were observed in the cell ultrastructure and their main parameters of membrane separation and linear extension were (9.6 ± 3.8) nm and (128 ± 63) nm, respectively.Our findings point to a process of privileged refilling of the ER, in which NCX and SOCE via the stromal interaction molecule (STIM)-Orai system are the sole protagonists. These results shed light on the molecular machinery involved in the function of a previously hypothesized subplasmalemmal Ca 2+ control unit during ER refilling with extracellular Ca 2+ .

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confidence: 56%

Section: Er Ca 2+ Is Refilled By Extracellular Ca 2+ Regardless Of Mementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Na⁺/Ca²⁺exchangers and Orai channels jointly refill endoplasmic reticulum (ER) Ca²⁺via ER nanojunctions in vascular endothelial cells

Giuro

Shrestha

Malli

et al. 2016

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“…22,26 At 1.25 mg/ml, there was a 98.3% reduction, but there may be a transient and reversible functional impairment of endothelial cell function. 24,26,34 At 2.5 mg/ml, there was a 99.8% reduction with no significant effect on corneal endothelial cell health. 26 At 4 mg/ml, there was a trend for decreased endothelial cells but minimal changes in mitochondrial function, and at significantly higher concentrations of 40 mg/ml, there was a significant reduction in endothelial cell density.…”

Section: Discussionmentioning

confidence: 89%

Cost-Effectiveness of Antifungal Supplementation of Corneal Cold Storage Media

2020

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Purpose: To evaluate the cost-effectiveness of supplementing hypothermic cold storage media (CSM) with antifungal therapy.Design: Cost-effectiveness analysis (CEA). Participant: Base case of a patient with Fuch's endothelial dystrophy undergoing a first eye keratoplasty. Methods: Cost-effective analysis of the base case with corneal tissue stored in CSM or CSM supplemented with antifungal therapy over a 16-year time horizon. Multiple clinical scenarios were considered, including endothelial keratoplasty (EK) and penetrating keratoplasty (PK); amphotericin B, voriconazole, caspofungin, and combination therapy; and third-party payer and societal perspectives. The incidences were derived from PubMed literature searches and average wholesale prices of medications; all costs were discounted 3% per annum and adjusted for inflation to 2019 US dollars.Main Outcome Measures: Incremental cost-effectiveness ratios (ICERs).Results: In the reference case, a corneal endothelial graft stored in amphotericin Besupplemented CSM was the most cost-effective approach from a third-party payer and societal perspective. Probability sensitivity analysis (PSA) of the societal model for the EK was robust, with 93.5% being below an arbitrary willingness-to-pay threshold (WTP) of $20 000 per fungal infection averted. Voriconazole, caspofungin, and combination antifungals were less cost-effective than amphotericin B. The main factors influencing the CEA were the incidences of postkeratoplasty fungal infections, potential increases in graft failures, and antifungal costs. For grafts intended for PKs, antifungal supplementation was less cost-effective than for EKs.Conclusions: Antifungal supplementation with amphotericin B for EK grafts was the most cost-effective approach of the studied antifungals; however, the CEA was sensitive to potential changes in graft failure rates, underlining the importance of long-term safety studies. For full-thickness corneal grafts, antifungal supplementation was less cost-effective.

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Na +/Ca2+ exchangers and Orai channels jointly refill endoplasmic reticulum (ER) Ca2+ via ER nanojunctions in vascular endothelial cells

Giuro

Shrestha

Malli

et al. 2017

Pflugers Arch - Eur J Physiol

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We investigated the role of Na+/ Ca2+ exchange (NCX) in the refilling of endoplasmic reticulum (ER) Ca2+ in vascular endothelial cells under various conditions of cell stimulation and plasma membrane (PM) polarization. Better understanding of the mechanisms behind basic ER Ca2+ content regulation is important, since current hypotheses on the possible ultimate causes of ER stress point to deterioration of the Ca2+ transport mechanism to/from ER itself. We measured [Ca2+]i temporal changes by Fura-2 fluorescence under experimental protocols that inhibit a host of transporters (NCX, Orai, non-selective transient receptor potential canonical (TRPC) channels, sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), Na+/ K+ ATPase (NKA)) involved in the Ca2+ communication between the extracellular space and the ER. Following histamine-stimulated ER Ca2+ release, blockade of NCX Ca2+-influx mode (by 10 μM KB-R7943) diminished the ER refilling capacity by about 40%, while in Orai1 dominant negative-transfected cells NCX blockade attenuated ER refilling by about 60%. Conversely, inhibiting the ouabain sensitive NKA (10 nM ouabain), which may be localized in PM-ER junctions, increased the ER Ca2+ releasable fraction by about 20%, thereby supporting the hypothesis that this process of privileged ER refilling is junction-mediated. Junctions were observed in the cell ultrastructure and their main parameters of membrane separation and linear extension were (9.6 ± 3.8) nm and (128 ± 63) nm, respectively. Our findings point to a process of privileged refilling of the ER, in which NCX and store-operated Ca2+ entry via the stromal interaction molecule (STIM)-Orai system are the sole protagonists. These results shed light on the molecular machinery involved in the function of a previously hypothesized subplasmalemmal Ca2+ control unit during ER refilling with extracellular Ca2+.Electronic supplementary material The online version of this article (doi:10.1007/s00424-017-1989-8) contains supplementary material, which is available to authorized users.

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Functional impairment of endothelial cells by the antimycotic amphotericin B

Cited by 3 publications

References 34 publications

Na⁺/Ca²⁺exchangers and Orai channels jointly refill endoplasmic reticulum (ER) Ca²⁺via ER nanojunctions in vascular endothelial cells

Na⁺/Ca²⁺exchangers and Orai channels jointly refill endoplasmic reticulum (ER) Ca²⁺via ER nanojunctions in vascular endothelial cells

Cost-Effectiveness of Antifungal Supplementation of Corneal Cold Storage Media

Na +/Ca2+ exchangers and Orai channels jointly refill endoplasmic reticulum (ER) Ca2+ via ER nanojunctions in vascular endothelial cells

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Functional impairment of endothelial cells by the antimycotic amphotericin B

Cited by 3 publications

References 34 publications

Na+/Ca2+exchangers and Orai channels jointly refill endoplasmic reticulum (ER) Ca2+via ER nanojunctions in vascular endothelial cells

Na+/Ca2+exchangers and Orai channels jointly refill endoplasmic reticulum (ER) Ca2+via ER nanojunctions in vascular endothelial cells

Cost-Effectiveness of Antifungal Supplementation of Corneal Cold Storage Media

Na +/Ca2+ exchangers and Orai channels jointly refill endoplasmic reticulum (ER) Ca2+ via ER nanojunctions in vascular endothelial cells

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Product

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Na⁺/Ca²⁺exchangers and Orai channels jointly refill endoplasmic reticulum (ER) Ca²⁺via ER nanojunctions in vascular endothelial cells

Na⁺/Ca²⁺exchangers and Orai channels jointly refill endoplasmic reticulum (ER) Ca²⁺via ER nanojunctions in vascular endothelial cells