Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Fuchs, R; Schraml, E; Leitinger, G; Letofsky-Papst, I; Stelzer, I; Haas, HS; Schauenstein, K; Sadjak, A.
á1-adrenergic drugs exhibit affinity to a thapsigargin-sensitive binding site and interfere with the intracellular Ca2+ homeostasis in human erythroleukemia cells.
Exp Cell Res. 2011; 317(20):2969-2980
Doi: 10.1016/j.yexcr.2011.08.003
Web of Science
PubMed
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FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Fuchs Robert
- Co-Autor*innen der Med Uni Graz
- Haas Helga Susanne
- Leitinger Gerd
- Sadjak Anton
- Schauenstein Konrad
- Schraml Elisabeth
- Stelzer Ingeborg
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- Abstract:
- Even though the erythroleukemia cell lines K562 and HEL do not express á1-adrenoceptors, some á1-adrenergic drugs influence both survival and differentiation of these cell lines. Since Ca2+ is closely related to cellular homeostasis, we examined the capacity of á1-adrenergic drugs to modulate the intracellular Ca2+ content in K562 cells. Because of morphological alterations of mitochondria following á1-adrenergic agonist treatment, we also scrutinized mitochondrial functions. In order to visualize the non-adrenoceptor binding site(s) of á1-adrenergic drugs in erythroleukemia cells, we evaluated the application of the fluorescent á1-adrenergic antagonist BODIPY® FL-Prazosin. We discovered that the á1-adrenergic agonists naphazoline, oxymetazoline and also the á1-adrenergic antagonist benoxathian are able to raise the intracellular Ca2+-content in K562 cells. Furthermore, we demonstrate that naphazoline treatment induces ROS-formation as well as an increase in ÄÏm in K562 cells. Using BODIPY® FL-Prazosin we were able to visualize the non-adrenoceptor binding site(s) of á1-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 á1-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 Ca2+.
Copyright © 2011 Elsevier Inc. All rights reserved. - Find related publications in this database (using NLM MeSH Indexing)
- Adrenergic Agents - pharmacology
- Adrenergic alpha-1 Receptor Agonists - pharmacology
- Adrenergic alpha-1 Receptor Antagonists - pharmacology
- Aging - drug effects
- Binding Sites - drug effects
- Calcium - metabolism
- Cell Death - drug effects
- Cell Differentiation - drug effects
- Cell Line, Tumor -
- Cell Survival - drug effects
- Homeostasis - drug effects
- Humans -
- K562 Cells -
- Leukemia, Erythroblastic, Acute - drug therapy
- Membrane Potential, Mitochondrial - drug effects
- Mitochondria - drug effects
- Mitochondrial Membranes - drug effects
- Naphazoline - pharmacology
- Reactive Oxygen Species - metabolism
- Receptors, Adrenergic, alpha-1 - metabolism
- Sarcoplasmic Reticulum Calcium-Transporting ATPases - antagonists and inhibitors
- Thapsigargin - pharmacology
- Find related publications in this database (Keywords)
- Erythroleukemia cells
- alpha 1-adrenergic drugs
- Mitochondria
- Calcium
- Reactive oxygen species