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Annals of Hematology

Erschienen in:

01.10.2009 | Original Article

The α1-adrenergic receptor antagonists, benoxathian and prazosin, induce apoptosis and a switch towards megakaryocytic differentiation in human erythroleukemia cells

verfasst von: Robert Fuchs, Ingeborg Stelzer, Helga S. Haas, Gerd Leitinger, Konrad Schauenstein, Anton Sadjak

Erschienen in: Annals of Hematology | Ausgabe 10/2009

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Abstract

The erythroleukemia cell lines K562 and human erythroleukemia (HEL) are established models to study erythroid and megakaryocytic differentiation in vitro. In this study, we show that the α1-adrenergic antagonists, benoxathian and prazosin, inhibit the proliferation and induce apoptosis in K562 and HEL cells. Furthermore, both tested substances induced the expression of the megakaryocytic marker CD41a, whereas the expression of the erythroid marker glycophorin-a was decreased or unchanged. Even though the expression of differentiation markers was similar after benoxathian and prazosin treatment in both cell lines, endomitosis of erythroleukemia cells was observed only after prazosin treatment. So far, benoxathian and prazosin are the first described extracellular ligands, which cause megakaryocytic differentiation in K562 and HEL cells. In summary, these results indicate a possible role of α1-adrenergic receptor signaling in the regulation of erythroid and megakaryocytic differentiation, even though the receptor dependence of the observed effects needs further investigation.

Spiegel A, Shivtiel S, Kalinkovich A et al (2007) Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34⁺ cells through Wnt signaling. Nat Immunol 8:1123–1131 doi:10.1038/ni1509 PubMedCrossRef

Katayama Y, Battista M, Kao WM et al (2006) Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell 124:407–421 doi:10.1016/j.cell.2005.10.041 PubMedCrossRef

Muthu K, Iyer S, He LK et al (2006) Murine hematopoietic stem cells and progenitors express adrenergic receptors. J Neuroimmunol 186:27–36 doi:10.1016/j.jneuroim.2007.02.007 CrossRef

Tang Y, Shankar R, Gamelli R, Jones S (1999) Dynamic norepinephrine alterations in bone marrow: evidence of functional innervation. J Neuroimmunol 96:182–189 doi:10.1016/S0165-5728(99)00032-6 PubMedCrossRef

Maestroni GJ (2000) Neurohormones and catecholamines as functional components of the bone marrow microenvironment. Ann N Y Acad Sci 917:29–37 (review)PubMedCrossRef

Maestroni GJ, Cosentio M, Marino F et al (1998) Neural and endogenous catecholamines in the bone marrow. Circadian association of norepinephrine with hematopoiesis? Exp Hematol 26:1172–1177PubMed

Brown JE, Adamson JW (1977) Modulation of in vitro erythropoiesis: the influence of β-adrenergic agonists on erythroid colony formation. J Clin Invest 60:70–77 doi:10.1172/JCI108771 PubMedCrossRef

Fonseca RB, Mohr AM, Wang L et al (2004) Adrenergic modulation of erythropoiesis following severe injury is mediated through bone marrow stroma. Surg Infect (Larchmt) 5:385–393 doi:10.1089/sur.2004.5.385 CrossRef

Andersson LC, Nilsson K, Gahmberg CG (1979) K562-a human erythroleukemic cell line. Int J Cancer 23:143–147 doi:10.1002/ijc.2910230202 PubMedCrossRef

10.

Martin P, Papayannopoulou T (1982) HEL cells: a new human erythroleukemia cell line with spontaneous and induced globin expression. Science 216:1233–1235 doi:10.1126/science.6177045 PubMedCrossRef

11.

Quentmeier H, MacLeod RA, Zaborski M, Drexler HG (2006) JAK2 V617F tyrosine kinase mutation in cell lines derived from myeloproliferative disorders. Leukemia 20:471–476 doi:10.1038/sj.leu.2404081 PubMedCrossRef

12.

James C, Ugo V, Le Couedic JP et al (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythemia vera. Nature 434:1144–1148 doi:10.1038/nature03546 PubMedCrossRef

13.

Gauwerky C, Golde DW (1980) Hormonal effects on cell proliferation in a human erythroleukemia cell line (K562). Blood 56:886–891PubMed

14.

He J, He Q (2005) Effects of prazosin on the proliferation and apoptosis of K562 leukemia cells. Zhong Nan Da Xue Xue Bao Yi Xue Ban 30:562–565PubMed

15.

Breton-Gorius J, Vainchenker W, Nurden A, Levy-Toledano S, Caen J (1981) Defective alpha-granule production in megakaryocytes from gray platelet syndrome: ultrastructural studies of bone marrow cells and megakaryocytes growing in culture from blood precursors. Am J Pathol 102:10–19PubMed

16.

Kakuta S, Ishikawa Y, Hashimoto T (1986) Morphological studies on the forming processes and patterns of the platelet demarcation membrane system in the megakaryocytic series of embryonic rat livers. Arch Histol Jpn 49:255–265 doi:10.1679/aohc.49.255 PubMedCrossRef

17.

Kikuchi J, Furukawa Y, Iwase S et al (1997) Polyploidization and functional maturation are two distinct processes during megakaryocytic differentiation: involvement of cyclin-dependent kinase inhibitor p21 in polyploidization. Blood 89:3980–3990PubMed

18.

Izaguirre V, Vargas M, Leon-Velarde F et al (1994) Inhibitory effect of an α1-adrenergic antagonist on erythropoiesis in normoxic or hypoxic mice. Int J Clin Lab Res 24:213–216 doi:10.1007/BF02592465 PubMedCrossRef

19.

Long MW, Heffner CH, Williams JL, Peters C, Prochownik EV (1990) Regulation of msegakaryocyte phenotype in human erythroleukemia cells. J Clin Invest 85:1072–1084 doi:10.1172/JCI114538 PubMedCrossRef

20.

Shelly C, Petruzzelli L, Herrara R (1998) PMA-induced phenotypic changes in K562 cells: MAPK-dependent and -independent events. Leukemia 12:1951–1961 doi:10.1038/sj.leu.2401221 PubMedCrossRef

21.

Zauli G, Gibellini D, Vitale M et al (1998) The induction of megakaryocyte differentiation is accompanied by selective Ser¹³³ phosphorylation of the transcription factor CREB in both HEL cell line and primary CD34⁺ cells. Blood 92:472–480PubMed

22.

Lerga A, Crespo P, Berciano M et al (1999) Regulation of c-myc and max in megakaryocytic and monocytic-macrophagic differentiation of K562 cells induced by protein kinase C modifiers: c-myc is down-regulated but does not inhibit differentiation. Cell Growth Differ 10:639–654PubMed

23.

Bermejo R, Vilaboa N, Cales C (2002) Regulation of CDC6, geminin, and CDT1 in human cells that undergo polyploidization. Mol Biol Cell 13:3989–4000 doi:10.1091/mbc.E02-04-0217 PubMedCrossRef

24.

Classen CF, Gnekow A, Debatin KM (2003) Terminal differentiation in vitro of patient-derived post-TMD megakaryoblastic AML cells. Ann Hematol 82:506–510 doi:10.1007/s00277-003-0692-3 PubMedCrossRef

25.

Alexandrov A, Keffel S, Goepel M, Michel MC (1998) Stimulation of α1A-adrenoreceptors in Rat-1 cells inhibits extracellular signal-regulated kinase by activating p38 mitogen activated protein kinase. Mol Pharmacol 54:755–760PubMed

26.

Hu ZW, Shi XY, Lin RZ, Hoffman BB (1999) Contrasting signalling pathways of α1A- and α1B-adrenergic receptor subtype activation of phosphatidylinositol 3-kinase and Ras in transfected NIH3T3 cells. Mol Endocrinol 13:3–14 doi:10.1210/me.13.1.3 PubMedCrossRef

27.

Xiao L, Pimental DR, Amin JK et al (2001) MEK1/2-ERK1/2 mediates α1-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes. J Mol Cell Cardiol 33:779–787 doi:10.1006/jmcc.2001.1348 PubMedCrossRef

28.

Waldrop BA, Mastalerz D, Piascik MT, Post GR (2002) α1A- and α1D-adrenergic receptors exhibit different requirements for agonist and mitogen-activated protein kinase activation to regulate growth responses in Rat1 fibroblasts. J Pharmacol Exp Ther 300:83–90 doi:10.1124/jpet.300.1.83 PubMedCrossRef

29.

Guerriero R, Parolini I, Testa U et al (2005) Inhibition of TPO-induced MEK or mTor activity induces opposite effects on the ploidy of human differentiating megakaryocytes. J Cell Sci 119:744–752 doi:10.1242/jcs.02784 CrossRef

30.

Jacquel A, Herrant M, Defamie V et al (2006) A survey of the signaling pathways involved in megakaryocytic differentiation of the human K562 leukemia cell line by molecular and c-DNA array analysis. Oncogene 25:781–794 doi:10.1038/sj.onc.1209119 PubMedCrossRef

31.

Lannutti BJ, Minear J, Blake N, Drachman JG (2006) Increased megakaryocytopoiesis in Lyn-deficient mice. Oncogene 25:3316–3324 doi:10.1038/sj.onc.1209351 PubMedCrossRef

32.

Zhu J, Taniguchi T, Takauji R et al (2000) Inverse agonism and neutral antagonism at a constitutively active alpha-1a adrenoreceptor. Br J Pharmacol 131:546–552 doi:10.1038/sj.bjp.0703584 PubMedCrossRef

33.

Gisbert R, Noguera MA, Ivorra MD, D’Ocon P (2000) Functional evidence of a constitutively active population of α1D-adrenoceptors in rat aorta. J Pharmacol Exp Ther 295:810–817PubMed

34.

Lin SC, Chueh SC, Hsiao CJ et al (2007) Prazosin displays anticancer activity against human prostate cancers: Targeting DNA and cell cycle. Neoplasia 9:830–839 doi:10.1593/neo.07475 PubMedCrossRef

Titel: The α1-adrenergic receptor antagonists, benoxathian and prazosin, induce apoptosis and a switch towards megakaryocytic differentiation in human erythroleukemia cells
verfasst von: Robert Fuchs
Ingeborg Stelzer
Helga S. Haas
Gerd Leitinger
Konrad Schauenstein
Anton Sadjak
Publikationsdatum: 01.10.2009
Verlag: Springer-Verlag
Erschienen in: Annals of Hematology / Ausgabe 10/2009
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-009-0704-z

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