Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1

We previously demonstrated that the translocase protein TSPO2 together with the voltage-dependent anion channel (VDAC) and adenine nucleotide transporter (ANT) were involved in a membrane transport complex in human red blood cells (RBCs). Because VDAC was proposed as a channel mediating ATP release...

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Autores principales: Marginedas-Freixa, I., Alvarez, C.L., Moras, M., Leal Denis, M.F., Hattab, C., Halle, F., Bihel, F., Mouro-Chanteloup, I., Lefevre, S.D., Le Van Kim, C., Schwarzbaum, P.J., Ostuni, M.A.
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Acceso en línea:http://hdl.handle.net/20.500.12110/paper_20452322_v8_n1_p_MarginedasFreixa
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
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spelling todo:paper_20452322_v8_n1_p_MarginedasFreixa2023-10-03T16:38:27Z Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1 Marginedas-Freixa, I. Alvarez, C.L. Moras, M. Leal Denis, M.F. Hattab, C. Halle, F. Bihel, F. Mouro-Chanteloup, I. Lefevre, S.D. Le Van Kim, C. Schwarzbaum, P.J. Ostuni, M.A. We previously demonstrated that the translocase protein TSPO2 together with the voltage-dependent anion channel (VDAC) and adenine nucleotide transporter (ANT) were involved in a membrane transport complex in human red blood cells (RBCs). Because VDAC was proposed as a channel mediating ATP release in RBCs, we used TSPO ligands together with VDAC and ANT inhibitors to test this hypothesis. ATP release was activated by TSPO ligands, and blocked by inhibitors of VDAC and ANT, while it was insensitive to pannexin-1 blockers. TSPO ligand increased extracellular ATP (ATPe) concentration by 24–59% over the basal values, displaying an acute increase in [ATPe] to a maximal value, which remained constant thereafter. ATPe kinetics were compatible with VDAC mediating a fast but transient ATP efflux. ATP release was strongly inhibited by PKC and PKA inhibitors as well as by depleting intracellular cAMP or extracellular Ca2+, suggesting a mechanism involving protein kinases. TSPO ligands favoured VDAC polymerization yielding significantly higher densities of oligomeric bands than in unstimulated cells. Polymerization was partially inhibited by decreasing Ca2+ and cAMP contents. The present results show that TSPO ligands induce polymerization of VDAC, coupled to activation of ATP release by a supramolecular complex involving VDAC, TSPO2 and ANT. © 2018, The Author(s). JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_20452322_v8_n1_p_MarginedasFreixa
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
description We previously demonstrated that the translocase protein TSPO2 together with the voltage-dependent anion channel (VDAC) and adenine nucleotide transporter (ANT) were involved in a membrane transport complex in human red blood cells (RBCs). Because VDAC was proposed as a channel mediating ATP release in RBCs, we used TSPO ligands together with VDAC and ANT inhibitors to test this hypothesis. ATP release was activated by TSPO ligands, and blocked by inhibitors of VDAC and ANT, while it was insensitive to pannexin-1 blockers. TSPO ligand increased extracellular ATP (ATPe) concentration by 24–59% over the basal values, displaying an acute increase in [ATPe] to a maximal value, which remained constant thereafter. ATPe kinetics were compatible with VDAC mediating a fast but transient ATP efflux. ATP release was strongly inhibited by PKC and PKA inhibitors as well as by depleting intracellular cAMP or extracellular Ca2+, suggesting a mechanism involving protein kinases. TSPO ligands favoured VDAC polymerization yielding significantly higher densities of oligomeric bands than in unstimulated cells. Polymerization was partially inhibited by decreasing Ca2+ and cAMP contents. The present results show that TSPO ligands induce polymerization of VDAC, coupled to activation of ATP release by a supramolecular complex involving VDAC, TSPO2 and ANT. © 2018, The Author(s).
format JOUR
author Marginedas-Freixa, I.
Alvarez, C.L.
Moras, M.
Leal Denis, M.F.
Hattab, C.
Halle, F.
Bihel, F.
Mouro-Chanteloup, I.
Lefevre, S.D.
Le Van Kim, C.
Schwarzbaum, P.J.
Ostuni, M.A.
spellingShingle Marginedas-Freixa, I.
Alvarez, C.L.
Moras, M.
Leal Denis, M.F.
Hattab, C.
Halle, F.
Bihel, F.
Mouro-Chanteloup, I.
Lefevre, S.D.
Le Van Kim, C.
Schwarzbaum, P.J.
Ostuni, M.A.
Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1
author_facet Marginedas-Freixa, I.
Alvarez, C.L.
Moras, M.
Leal Denis, M.F.
Hattab, C.
Halle, F.
Bihel, F.
Mouro-Chanteloup, I.
Lefevre, S.D.
Le Van Kim, C.
Schwarzbaum, P.J.
Ostuni, M.A.
author_sort Marginedas-Freixa, I.
title Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1
title_short Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1
title_full Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1
title_fullStr Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1
title_full_unstemmed Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1
title_sort human erythrocytes release atp by a novel pathway involving vdac oligomerization independent of pannexin-1
url http://hdl.handle.net/20.500.12110/paper_20452322_v8_n1_p_MarginedasFreixa
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