Identification of the Ca²âº entry pathway involved in deoxygenation-induced phosphatidylserine exposure in red blood cells from patients with sickle cell disease.
Pflugers Arch
; 465(11): 1651-60, 2013 Nov.
Article
en En
| MEDLINE
| ID: mdl-23775402
ABSTRACT
Phosphatidylserine (PS) exposure in red blood cells (RBCs) from sickle cell disease (SCD) patients is increased compared to levels in normal individuals and may participate in the anaemic and ischaemic complications of SCD. Exposure is increased by deoxygenation and occurs with elevation of intracellular Ca²âº to low micromolar levels. The Ca²âº entry step has not been defined but a role for the deoxygenation-induced pathway, Psickle, is postulated. Partial Psickle inhibitors 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS), 4,4'-dithiocyano-2,2'-stilbene-disulphonic acid (DIDS) and dipyridamole inhibited deoxygenation-induced PS exposure (DIDS IC50, 118 nM). Inhibitors and activators of other pathways (including these stimulated by depolarisation, benzodiazepines, glutamate and stretch) were without effect. Zn²âº and Gd³âº stimulated PS exposure to high levels. In the case of Zn²âº, this effect was independent of oxygen (and hence HbS polymerisation and RBC sickling) but required extracellular Ca²âº. The effect was completely abolished when Zn²âº (100 µM) was added to RBCs suspended in autologous plasma, implying a requirement of high levels of free Zn²âº.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oxígeno
/
Fosfatidilserinas
/
Calcio
/
Eritrocitos Anormales
/
Anemia de Células Falciformes
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Pflugers Arch
Año:
2013
Tipo del documento:
Article
País de afiliación:
Reino Unido