alpha 1-adrenergic drugs modulate differentiation and cell death of human erythroleukemia cells through non adrenergic mechanism

作者：Fuchs Robert^*; Schraml Elisabeth; Leitinger Gerd; Stelzer Ingeborg; Allard Nathalie; Haas Helga Susanne; Schauenstein Konrad; Sadjak Anton

来源：Experimental Cell Research, 2011, 317(16): 2239-2251.

DOI：10.1016/j.yexcr.2011.07.005

• Erythroleukemia cells
• Erythroid progenitor cells
• alpha 1-adrenergic drugs
• Cell death
• Differentiation

Preliminary data showed that alpha 1-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 alpha 1-adrenergic signalling, we examined alpha 1-adrenoceptor expression of erythroleukemia cells and compared the in vitro effects of alpha-adrenergic antagonists with those of agonists. We discovered that alpha 1-adrenergic agonists suppress both erythroid differentiation and growth of erythroleukemia cells concomitant with lipofuscin accumulation, autophagy and necrotic cell death. alpha 1-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 alpha 1-adrenoceptors, even though agonists and antagonists displayed opposing effects regarding cellular growth and differentiation of erythroleukemia cells. Our data suggest that the effects of alpha 1-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.

• 出版日期2011-10-1