Lysophosphatidic acid-activated calcium signaling is elevated in red cells from sickle cell disease patients

Mostrar todas las versiones(2)

Abstract: (1) Background: It is known that sickle cells contain a higher amount of Ca2+ compared to healthy red blood cells (RBCs). The increased Ca2+ is associated with the most severe symptom of sickle cell disease (SCD), the vaso-occlusive crisis (VOC). The Ca2+ entry pathway received the name...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Jue, Hertz, Laura, Ruppenthal, Sandra, El Nemer, Wassim, Connes, Philippe, Goede, Jeroen S., Bogdanova, Anna, Birnbaumer, Lutz, Kaestner, Lars
Formato: Artículo
Lenguaje:Inglés
Publicado: MDPI 2021
Materias:
ENFERMEDAD DE CELULAS FALCIFORMES
ERITROCITOS
HISTOLOGIA
CALCIO
ANEMIA HEMOLITICA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/11619
https://doi.org/10.3390/cells10020456
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-11619
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic ENFERMEDAD DE CELULAS FALCIFORMES
ERITROCITOS
HISTOLOGIA
CALCIO
ANEMIA HEMOLITICA
spellingShingle ENFERMEDAD DE CELULAS FALCIFORMES
ERITROCITOS
HISTOLOGIA
CALCIO
ANEMIA HEMOLITICA
Wang, Jue
Hertz, Laura
Ruppenthal, Sandra
El Nemer, Wassim
Connes, Philippe
Goede, Jeroen S.
Bogdanova, Anna
Birnbaumer, Lutz
Kaestner, Lars
Lysophosphatidic acid-activated calcium signaling is elevated in red cells from sickle cell disease patients
topic_facet ENFERMEDAD DE CELULAS FALCIFORMES
ERITROCITOS
HISTOLOGIA
CALCIO
ANEMIA HEMOLITICA
description Abstract: (1) Background: It is known that sickle cells contain a higher amount of Ca2+ compared to healthy red blood cells (RBCs). The increased Ca2+ is associated with the most severe symptom of sickle cell disease (SCD), the vaso-occlusive crisis (VOC). The Ca2+ entry pathway received the name of Psickle but its molecular identity remains only partly resolved. We aimed to map the involved Ca2+ signaling to provide putative pharmacological targets for treatment. (2) Methods: The main technique applied was Ca2+ imaging of RBCs from healthy donors, SCD patients and a number of transgenic mouse models in comparison to wild-type mice. Life-cell Ca2+ imaging was applied to monitor responses to pharmacological targeting of the elements of signaling cascades. Infection as a trigger of VOC was imitated by stimulation of RBCs with lysophosphatidic acid (LPA). These measurements were complemented with biochemical assays. (3) Results: Ca2+ entry into SCD RBCs in response to LPA stimulation exceeded that of healthy donors. LPA receptor 4 levels were increased in SCD RBCs. Their activation was followed by the activation of Gi protein, which in turn triggered opening of TRPC6 and CaV2.1 channels via a protein kinase C and a MAP kinase pathway, respectively. (4) Conclusions: We found a new Ca2+ signaling cascade that is increased in SCD patients and identified new pharmacological targets that might be promising in addressing the most severe symptom of SCD, the VOC.
format Artículo
author Wang, Jue
Hertz, Laura
Ruppenthal, Sandra
El Nemer, Wassim
Connes, Philippe
Goede, Jeroen S.
Bogdanova, Anna
Birnbaumer, Lutz
Kaestner, Lars
author_facet Wang, Jue
Hertz, Laura
Ruppenthal, Sandra
El Nemer, Wassim
Connes, Philippe
Goede, Jeroen S.
Bogdanova, Anna
Birnbaumer, Lutz
Kaestner, Lars
author_sort Wang, Jue
title Lysophosphatidic acid-activated calcium signaling is elevated in red cells from sickle cell disease patients
title_short Lysophosphatidic acid-activated calcium signaling is elevated in red cells from sickle cell disease patients
title_full Lysophosphatidic acid-activated calcium signaling is elevated in red cells from sickle cell disease patients
title_fullStr Lysophosphatidic acid-activated calcium signaling is elevated in red cells from sickle cell disease patients
title_full_unstemmed Lysophosphatidic acid-activated calcium signaling is elevated in red cells from sickle cell disease patients
title_sort lysophosphatidic acid-activated calcium signaling is elevated in red cells from sickle cell disease patients
publisher MDPI
publishDate 2021
url https://repositorio.uca.edu.ar/handle/123456789/11619
https://doi.org/10.3390/cells10020456
work_keys_str_mv AT wangjue lysophosphatidicacidactivatedcalciumsignalingiselevatedinredcellsfromsicklecelldiseasepatients
AT hertzlaura lysophosphatidicacidactivatedcalciumsignalingiselevatedinredcellsfromsicklecelldiseasepatients
AT ruppenthalsandra lysophosphatidicacidactivatedcalciumsignalingiselevatedinredcellsfromsicklecelldiseasepatients
AT elnemerwassim lysophosphatidicacidactivatedcalciumsignalingiselevatedinredcellsfromsicklecelldiseasepatients
AT connesphilippe lysophosphatidicacidactivatedcalciumsignalingiselevatedinredcellsfromsicklecelldiseasepatients
AT goedejeroens lysophosphatidicacidactivatedcalciumsignalingiselevatedinredcellsfromsicklecelldiseasepatients
AT bogdanovaanna lysophosphatidicacidactivatedcalciumsignalingiselevatedinredcellsfromsicklecelldiseasepatients
AT birnbaumerlutz lysophosphatidicacidactivatedcalciumsignalingiselevatedinredcellsfromsicklecelldiseasepatients
AT kaestnerlars lysophosphatidicacidactivatedcalciumsignalingiselevatedinredcellsfromsicklecelldiseasepatients
bdutipo_str Repositorios
_version_ 1764820525116293120

Ejemplares similares