Kinetic properties of cation/H+-exchange: calcimycin (A23187)-mediated Ca2+/2H+-exchange on the bilayer lipid membrane

Pohl, Peter; Antonenko, Yuri N.; Yaguzhinsky, L. S.

doi:10.1016/0005-2736(90)90321-e

Cited by 22 publications

(15 citation statements)

References 31 publications

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“…27 Additionally, previous studies have shown that the optimal pH for A23187 mediated transport of Mn 2þ is 6.7-7.0. 28,29 Consequently, the pH of the loading mixture and ionophore concentration might be expected to have a significant impact on drug transport and the rate of drug loading into liposomes. Figure 1C shows the effect of pH on VRL loading at an initial D/L ratio of 0.3 wt/wt (608C, 0.35 mg A23187/mg lipid).…”

Section: Optimization Of Vrl Loading Conditions In Sm/chol Liposomesmentioning

confidence: 99%

Optimization and Characterization of a Sphingomyelin/Cholesterol Liposome Formulation of Vinorelbine with Promising Antitumor Activity

Semple¹,

Leone²,

Wang³

et al. 2005

Journal of Pharmaceutical Sciences

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Section: Optimization Of Vrl Loading Conditions In Sm/chol Liposomesmentioning

confidence: 99%

Optimization and Characterization of a Sphingomyelin/Cholesterol Liposome Formulation of Vinorelbine with Promising Antitumor Activity

Semple¹,

Leone²,

Wang³

et al. 2005

Journal of Pharmaceutical Sciences

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“…Pretreating the platelets with 5 mol/L CsA for 3 minutes did not significantly change the kinetics of ⌬⌿m loss induced by A23187 (gray line in Figure 1A-a). This instantaneous loss of ⌬⌿m was probably attributable to insertion of Ca 2ϩ -ionophore in the mitochondrial membrane, transporting Ca 2ϩ ions down their electrochemical gradient via H ϩ exchange, 24 thus dissipating the transmembrane proton gradient similarly to CCCP. ⌬⌿m loss also occurred when TG was added to platelets (black line in Figure 1A-b).…”

Section: ؉mentioning

confidence: 99%

Rapid Procoagulant Phosphatidylserine Exposure Relies on High Cytosolic Calcium Rather Than on Mitochondrial Depolarization

Arachiche

Kerbiriou-Nabias

Garcin

et al. 2009

ATVB

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Objective-Relationships between intracellular Ca 2ϩ concentration ([Ca 2ϩ ] cyt ) and apoptotic events, such as mitochondrial depolarization (⌬⌿m loss) and Bcl-2 and Bad phosphorylation, were analyzed in platelets and Jurkat cells in relation to rapid procoagulant phosphatidylserine (PS) exposure. Methods and Results-Platelets were stimulated with A23187, thapsigargin (TG) and thrombin plus convulxin (Thr/Cvx), andJurkat cells with ionomycin, in the presence or absence of cyclosporin A (CsA), a mitochondrial permeability transition pore inhibitor. ⌬⌿m loss occurred when platelets were stimulated in Ca 2ϩ medium in conditions exposing PS, but also in EGTA medium. CsA inhibited PS exposure, [Ca 2ϩ ] cyt increase, and ⌬⌿m loss in platelets stimulated with TG and Thr/Cvx, but had no inhibitory effect on A23187 stimulation. CsA reduced TG-induced Ca 2ϩ release from the endoplasmic reticulum and, consequently, external Ca 2ϩ influx. In ionomycin-stimulated Jurkat cells, rapid PS exposure was evidenced but not ⌬⌿m loss, and CsA did not inhibit the process. The status of phosphorylated Bad and Bcl-2 in both cell types remained unchanged on stimulation. Conclusions-Whether ⌬⌿m loss occurs or not, PS exposure is triggered by a high [Ca 2ϩ ] cyt increase. Data further demonstrate that CsA prevents membrane scrambling by inhibiting the high [Ca 2ϩ ] cyt increase, independently of its effect on mitochondrial permeability transition pore. Key Words: platelets Ⅲ Jurkat Ⅲ apoptosis Ⅲ procoagulant phosphatidylserine Ⅲ thrombin plus convulxin P hospholipid scrambling, leading to phosphatidylserine (PS) exposure to the external leaflet of cell membranes, characterizes blood platelet procoagulant activation. The essential role of phospholipid reorganization on the surface of stimulated blood cells is illustrated by the existence of Scott syndrome, a rare bleeding disorder caused by defective membrane scrambling in platelets and hematopoietic cells such as lymphocytes (reviewed in 1 ).PS exposure also characterizes apoptosis and occurs during platelet storage with other typical morphological and biochemical features of apoptosis (reviewed in 2 ), including loss of the mitochondrial transmembrane potential (⌬⌿m). [3][4][5] ⌬⌿m loss is caused by opening of a channel, the mitochondrial permeability transition pore (mPTP), and requires an increase in mitochondrial Ca 2ϩ . 6 The mPTP is composed of several proteins, including the adenine nucleotide translocator (ANT), the voltage-dependent anion channel, and cyclophilin D (CypD). 7 mPTP opening is blocked by cyclosporin A (CsA), which binds to CypD and dissociates it from the translocator. 8 In platelets, the physiological procoagulant activity is triggered by dual agonist stimulation with thrombin (Thr) plus convulxin (Cvx), the latter stimulating GPVI, a platelet collagen receptor. 9 This leads a subpopulation of platelets, named coated-platelets, to express PS and high levels of several procoagulant proteins on their surface. 10 Studies have shown that both ⌬⌿m loss and ...

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“…There are difficulties in comparing our results with those in the literature, however. Although a number of studies have appeared that discuss aspects of A23187-mediated transport of multivalent cations across the walls of lipid bilayervesicles (Blau et al, 1984;Hunt et al, 1978;Kolber and Haynes, 1981;Pohl et al, 1980;Pohl et al, 1990;Shastri et al, 19871, initial permeabilities of the type reported here have never been published previously for vesicles. Ion transport data typically were gathered over at least several minutes for the calculation of time-averaged kinetic properties, and the influence of a changing transmembrane cation concentration gradient or electropotential could not always be ruled out.…”

Section: Effect Of Ph Onmentioning

confidence: 79%

“…Hamilton and Kaler (l987,1990a,b) theorized that vesicles could be used as separation media on the basis of their work on the permeability of synthetic surfactant vesicular membranes to Na+ and K+ in the presence and absence of synthetic, crown ether ionophores. Also, it has been shown that EDTA can be used to concentrate divalent cations in phosphatidylcholine vesicles (Pohl et al, 1980) and to increase the flux of Ca2+ across planar bilayer lipid membranes (Pohl et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Biomimetic Metal‐Sorbing Vesicles: Cd²+ Uptake by Phosphatidylcholine Vesicles Doped with Ionophore A23187

Zanten¹,

Monbouquette²

1992

Biotechnology Progress

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Unilamellar phosphatidylcholine vesicles, harboring the ionophore, A23187, in the bilayer and the water-soluble chelating agent, nitrilotriacetate, in the vesicle interior, rapidly sequester and concentrate Cd2+ from dilute aqueous solution. Metal-sorbing vesicle permeabilities for cadmium ion at 5 ppm (42.8 microM) ranged from 8.09 x 10(-7) to 1.27 x 10(-4) cm/s for surface A23187 concentrations of 0.22-2.27 pmol/cm2 (which correspond to lipid:carrier molar ratios of 2000:1 to 200:1) and pH's from 5.5 to 8.5. The Cd2+ permeability shows linear variation with carrier concentration under the conditions studied. As pH is decreased, an increasing fraction of the A23187 becomes protonated, and the permeability exhibits a positive linear relationship with a function related to that for the fraction of unprotonated carrier. These noncovalently assembled, metal-sorbing vesicles exhibit shelf lives of several months and remain stable throughout typical metal sorption studies.

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Kinetic properties of cation/H+-exchange: calcimycin (A23187)-mediated Ca2+/2H+-exchange on the bilayer lipid membrane

Cited by 22 publications

References 31 publications

Optimization and Characterization of a Sphingomyelin/Cholesterol Liposome Formulation of Vinorelbine with Promising Antitumor Activity

Optimization and Characterization of a Sphingomyelin/Cholesterol Liposome Formulation of Vinorelbine with Promising Antitumor Activity

Rapid Procoagulant Phosphatidylserine Exposure Relies on High Cytosolic Calcium Rather Than on Mitochondrial Depolarization

Biomimetic Metal‐Sorbing Vesicles: Cd²+ Uptake by Phosphatidylcholine Vesicles Doped with Ionophore A23187

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Kinetic properties of cation/H+-exchange: calcimycin (A23187)-mediated Ca2+/2H+-exchange on the bilayer lipid membrane

Cited by 22 publications

References 31 publications

Optimization and Characterization of a Sphingomyelin/Cholesterol Liposome Formulation of Vinorelbine with Promising Antitumor Activity

Optimization and Characterization of a Sphingomyelin/Cholesterol Liposome Formulation of Vinorelbine with Promising Antitumor Activity

Rapid Procoagulant Phosphatidylserine Exposure Relies on High Cytosolic Calcium Rather Than on Mitochondrial Depolarization

Biomimetic Metal‐Sorbing Vesicles: Cd2+ Uptake by Phosphatidylcholine Vesicles Doped with Ionophore A23187

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Product

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Biomimetic Metal‐Sorbing Vesicles: Cd²+ Uptake by Phosphatidylcholine Vesicles Doped with Ionophore A23187