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Titel: Lysophosphatidic Acid-Activated Calcium Signaling Is Elevated in Red Cells from Sickle Cell Disease Patients
VerfasserIn: Wang, Jue
Hertz, Laura
Ruppenthal, Sandra
El Nemer, Wassim
Connes, Philippe
Goede, Jeroen S.
Bogdanova, Anna
Birnbaumer, Lutz
Kaestner, Lars
Sprache: Englisch
Titel: Cells
Bandnummer: 10
Heft: 2
Verlag/Plattform: MDPI
Erscheinungsjahr: 2021
Freie Schlagwörter: erythrocytes
sickle cell disease
LPA receptor
G protein signaling
transgenic mice
protein kinase Cα
MAP kinase
TRPC6
CaV2.1
Gárdos channel
DDC-Sachgruppe: 500 Naturwissenschaften
530 Physik
610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
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 Cα 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.
DOI der Erstveröffentlichung: 10.3390/cells10020456
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-339542
hdl:20.500.11880/31250
http://dx.doi.org/10.22028/D291-33954
ISSN: 2073-4409
Datum des Eintrags: 28-Apr-2021
Bezeichnung des in Beziehung stehenden Objekts: Supplementary Material
In Beziehung stehendes Objekt: https://www.mdpi.com/2073-4409/10/2/456/s1
Fakultät: M - Medizinische Fakultät
NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: M - Anatomie und Zellbiologie
M - Frauenheilkunde
NT - Physik
Professur: M - Prof. Dr. Peter Lipp
NT - Prof. Dr. Christian Wagner
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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