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Gewählte Publikation:

Fuchs, R; Schraml, E; Leitinger, G; Letofsky-Papst, I; Stelzer, I; Haas, HS; Schauenstein, K; Sadjak, A.
(2011): alpha 1-adrenergic drugs exhibit affinity to a thapsigargin-sensitive binding site and interfere with the intracellular Ca(2+) homeostasis in human erythroleukemia cells
EXP CELL RES. 2011; 317(20): 2969-2980. FullText FullText_BOKU

Abstract:
Even though the erythroleukemia cell lines K562 and HEL do not express alpha 1-adrenoceptors, some alpha 1-adrenergic drugs influence both survival and differentiation of these cell lines. Since Ca(2+) is closely related to cellular homeostasis, we examined the capacity of alpha 1-adrenergic drugs to modulate the intracellular Ca(2+) content in K562 cells. Because of morphological alterations of mitochondria following alpha 1-adrenergic agonist treatment, we also scrutinized mitochondrial functions. In order to visualize the non-adrenoceptor binding site(s) of alpha 1-adrenergic drugs in erythroleukemia cells, we evaluated the application of the fluorescent alpha 1-adrenergic antagonist BODIPY (R) FL-Prazosin. We discovered that the alpha 1-adrenergic agonists naphazoline, oxymetazoline and also the alpha 1-adrenergic antagonist benoxathian are able to raise the intracellular Ca(2+)-content in K562 cells. Furthermore, we demonstrate that naphazoline treatment induces ROS-formation as well as an increase in Delta psi m in K562 cells. Using BODIPY (R) FL-Prazosin we were able to visualize the non-adrenoceptor binding site(s) of alpha 1-adrenergic drugs in erythroleukemia cells. Interestingly, the SERCA-inhibitor thapsigargin appears to interfere with the binding of BODIPY FL-Prazosin. Our data suggest that the effects of alpha 1-adrenergic drugs on erythroleukemia cells are mediated by a thapsigargin sensitive binding site, which controls the fate of erythroleukemia cells towards differentiation, senescence and cell death through modulation of intracellular Ca(2+). (C) 2011 Elsevier Inc. All rights reserved.
Autor*innen der BOKU Wien:
Schraml Elisabeth
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Find related publications in this database (Keywords)
Erythroleukemia cells
alpha 1-adrenergic drugs
Mitochondria
Calcium
Reactive oxygen species


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