info:eu-repo/semantics/article
Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1
Fecha
2018-12Registro en:
Marginedas Freixa, Irene; Alvarez, Cora Lilia; Moras, Martina; Leal Denis, Maria Florencia; Hattab, Claude; et al.; Human erythrocytes release ATP by a novel pathway involving VDAC oligomerization independent of pannexin-1; Springer Nature; Scientific Reports; 8; 1; 12-2018; 1-13
2045-2322
CONICET Digital
CONICET
Autor
Marginedas Freixa, Irene
Alvarez, Cora Lilia
Moras, Martina
Leal Denis, Maria Florencia
Hattab, Claude
Halle, François
Bihel, Frédéric
Mouro Chanteloup, Isabelle
Lefevre, Sophie Denise
Le Van Kim, Caroline
Schwarzbaum, Pablo Julio
Ostuni, Mariano
Resumen
We previously demonstrated that the translocase protein TSPO2 together with the voltage-dependentanion channel (VDAC) and adenine nucleotide transporter (ANT) were involved in a membrane transportcomplex in human red blood cells (RBCs). Because VDAC was proposed as a channel mediating ATPrelease 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 wasinsensitive 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 remainedconstant thereafter. ATPe kinetics were compatible with VDAC mediating a fast but transient ATPefflux. ATP release was strongly inhibited by PKC and PKA inhibitors as well as by depleting intracellularcAMP or extracellular Ca2+, suggesting a mechanism involving protein kinases. TSPO ligands favouredVDAC polymerization yielding significantly higher densities of oligomeric bands than in unstimulatedcells. Polymerization was partially inhibited by decreasing Ca2+ and cAMP contents. The present resultsshow that TSPO ligands induce polymerization of VDAC, coupled to activation of ATP release by asupramolecular complex involving VDAC, TSPO2 and ANT.