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doi:10.22028/D291-33954
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 |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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cells-10-00456-v3.pdf | 4,53 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons