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; Stelzer, I; Allard, N; Haas, HS; Schauenstein, K; Sadjak, A.
á1-Adrenergic drugs modulate differentiation and cell death of human erythroleukemia cells through non adrenergic mechanism.
Exp Cell Res. 2011; 317(16):2239-2251
Doi: 10.1016/j.yexcr.2011.07.005
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
- Meier-Allard Nathalie
- Sadjak Anton
- Schauenstein Konrad
- Schraml Elisabeth
- Stelzer Ingeborg
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- Abstract:
- Preliminary data showed that á1-adrenergic antagonists induce apoptosis and a switch towards megakaryocytic differentiation in human erythroleukemia cells. To test the hypothesis whether survival and differentiation of erythroleukemia cells are under control of á1-adrenergic signalling, we examined á1-adrenoceptor expression of erythroleukemia cells and compared the in vitro effects of á-adrenergic antagonists with those of agonists. We discovered that á1-adrenergic agonists suppress both erythroid differentiation and growth of erythroleukemia cells concomitant with lipofuscin accumulation, autophagy and necrotic cell death. á1-adrenergic agonists also inhibit the in vitro growth of physiologic hematopoietic progenitors obtained from umbilical cord blood with high selectivity for the erythroid lineage. Interestingly, the observed effects could not be related to á1-adrenoceptors, even though agonists and antagonists displayed opposing effects regarding cellular growth and differentiation of erythroleukemia cells. Our data suggest that the effects of á1-adrenergic drugs are related to a non-adrenoceptor binding site, controlling the fate of erythroid progenitor cells towards differentiation and cell death. Since the observed effects are not mediated through adrenoceptors, the physiologic relevance of our data remains unclear, so far. Nevertheless, the identification of the still unknown binding site(s) might disclose new insights into regulation of erythroid differentiation and cell death.
Copyright © 2011 Elsevier Inc. All rights reserved. - Find related publications in this database (using NLM MeSH Indexing)
- Adrenergic alpha-1 Receptor Agonists - pharmacology
- Adrenergic alpha-Agonists - pharmacology
- Adrenergic alpha-Antagonists - pharmacology
- Antigens, CD45 - metabolism
- Apoptosis - drug effects
- Autophagy - drug effects
- Caspase 3 - metabolism
- Cell Aggregation - drug effects
- Cell Death - drug effects
- Cell Differentiation - drug effects
- Cell Line, Tumor -
- Cell Proliferation - drug effects
- Cell Survival - drug effects
- Drug Interactions -
- Erythroid Cells - cytology
- Erythroid Precursor Cells - cytology
- Fetal Blood - cytology
- Gene Expression - drug effects
- Glycophorin - metabolism
- Hemin - pharmacology
- Hemoglobins - metabolism
- Humans -
- Hydrogen-Ion Concentration - drug effects
- K562 Cells -
- Leukemia, Erythroblastic, Acute - metabolism
- Megakaryocyte Progenitor Cells - cytology
- Megakaryocytes - cytology
- Naphazoline - pharmacology
- Necrosis - chemically induced
- Oxathiins - pharmacology
- Prazosin - pharmacology
- Receptors, Adrenergic, alpha-1 - genetics
- Find related publications in this database (Keywords)
- Erythroleukemia cells
- Erythroid progenitor cells
- alpha 1-adrenergic drugs
- Cell death
- Differentiation