Emodin Can Induce K562 Cells to Erythroid Differentiation and Improve the Expression of Globin Genes

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2013 Jun 8

PMID 23744534

Citations 17

Authors

Yan-Ni Ma

Ming-Tai Chen

Zhi-Kui Wu

Hua-Lu Zhao

Hai-Chuan Yu

Jia Yu

Jun-Wu Zhang

Affiliations

Soon will be listed here.

Abstract

In China, the traditional Chinese medicine "YiSui ShenXu Granule" has been used for treating β-thalassemia over 20 years and known to be effective in clinic. Several purified components from "YiSui ShenXu Granule" are tested in K562 cells to reveal its effect on globin expression and erythroid differentiation, and one of the purified components, emodin, was demonstrated to increase the expression of α-, ε-, γ-globin, CD235a, and CD71 in K562 cells. Moreover, the increase of their expression is emodin concentration-dependent. The mRNA and microRNA (miRNA) expression profiles are further analyzed and 417 mRNAs and 35 miRNAs with differential expression between untreated and emodin-treated K562 cells were identified. Among them, two mRNAs that encode known positive regulators of erythropoiesis, ALAS2, and c-KIT respectively, increased during emodin-induced K562 erythroid differentiation, meanwhile, two negative regulators, miR-221 and miR-222, decreased during this process. These results indicate that emodin can improve the expression of globin genes in K562 cells and also induce K562 cells to erythroid differentiation possibly through up-regulating ALAS2 and c-KIT and down-regulating miR-221 and miR-222.

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References

Zhang C, Wu Z . Molecular pharmacological basis of the YiSui ShenXu Granule in beta-thalassemia therapy. J Ethnopharmacol. 2008; 120(3):437-41. DOI: 10.1016/j.jep.2008.09.024. View

Duff C, Smith-Miles K, Lopes L, Tian T . Mathematical modelling of stem cell differentiation: the PU.1-GATA-1 interaction. J Math Biol. 2011; 64(3):449-68. DOI: 10.1007/s00285-011-0419-3. View

Kramer M, Gunaratne P, Ferreira G . Transcriptional regulation of the murine erythroid-specific 5-aminolevulinate synthase gene. Gene. 2000; 247(1-2):153-66. DOI: 10.1016/s0378-1119(00)00103-7. View

Kaneko H, Shimizu R, Yamamoto M . GATA factor switching during erythroid differentiation. Curr Opin Hematol. 2010; 17(3):163-8. DOI: 10.1097/MOH.0b013e32833800b8. View

Gabbianelli M, Testa U, Morsilli O, Pelosi E, Saulle E, Petrucci E . Mechanism of human Hb switching: a possible role of the kit receptor/miR 221-222 complex. Haematologica. 2010; 95(8):1253-60. PMC: 2913072. DOI: 10.3324/haematol.2009.018259. View

Felli N, Fontana L, Pelosi E, Botta R, Bonci D, Facchiano F . MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci U S A. 2005; 102(50):18081-6. PMC: 1312381. DOI: 10.1073/pnas.0506216102. View

Filipe A, Li Q, Deveaux S, Godin I, Romeo P, Stamatoyannopoulos G . Regulation of embryonic/fetal globin genes by nuclear hormone receptors: a novel perspective on hemoglobin switching. EMBO J. 1999; 18(3):687-97. PMC: 1171161. DOI: 10.1093/emboj/18.3.687. View

Yokomizo T, Hasegawa K, Ishitobi H, Osato M, Ema M, Ito Y . Runx1 is involved in primitive erythropoiesis in the mouse. Blood. 2008; 111(8):4075-80. DOI: 10.1182/blood-2007-05-091637. View

Ley T, DESIMONE J, Anagnou N, Keller G, Humphries R, Turner P . 5-azacytidine selectively increases gamma-globin synthesis in a patient with beta+ thalassemia. N Engl J Med. 1982; 307(24):1469-75. DOI: 10.1056/NEJM198212093072401. View

10.

Aerbajinai W, Zhu J, Kumkhaek C, Chin K, Rodgers G . SCF induces gamma-globin gene expression by regulating downstream transcription factor COUP-TFII. Blood. 2009; 114(1):187-94. PMC: 2927201. DOI: 10.1182/blood-2008-07-170712. View

11.

Macfarlane L, Murphy P . MicroRNA: Biogenesis, Function and Role in Cancer. Curr Genomics. 2011; 11(7):537-61. PMC: 3048316. DOI: 10.2174/138920210793175895. View

12.

Feng Y, Huang S, Dou W, Zhang S, Chen J, Shen Y . Emodin, a natural product, selectively inhibits 11beta-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice. Br J Pharmacol. 2010; 161(1):113-26. PMC: 2962821. DOI: 10.1111/j.1476-5381.2010.00826.x. View

13.

Kawano T, Horiguchi-Yamada J, Saito S, Iwase S, Furukawa Y, Kano Y . Ectopic cyclin D1 expression blocks STI571-induced erythroid differentiation of K562 cells. Leuk Res. 2004; 28(6):623-9. DOI: 10.1016/j.leukres.2003.10.022. View

14.

Whatley S, Ducamp S, Gouya L, Grandchamp B, Beaumont C, Badminton M . C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload. Am J Hum Genet. 2008; 83(3):408-14. PMC: 2556430. DOI: 10.1016/j.ajhg.2008.08.003. View

15.

Wang D, Li Y, Shen B . A novel erythroid differentiation related gene EDRF1 upregulating globin gene expression in HEL cells. Chin Med J (Engl). 2003; 115(11):1701-5. View

16.

Perrine S, Miller B, Faller D, Cohen R, Vichinsky E, Hurst D . Sodium butyrate enhances fetal globin gene expression in erythroid progenitors of patients with Hb SS and beta thalassemia. Blood. 1989; 74(1):454-9. View

17.

Bakker W, Blazquez-Domingo M, Kolbus A, Besooyen J, Steinlein P, Beug H . FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1. J Cell Biol. 2004; 164(2):175-84. PMC: 2172323. DOI: 10.1083/jcb.200307056. View

18.

Kucerova J, Horvathova M, Mojzikova R, Belohlavkova P, cermak J, Divoky V . New mutation in erythroid-specific delta-aminolevulinate synthase as the cause of X-linked sideroblastic anemia responsive to pyridoxine. Acta Haematol. 2011; 125(4):193-7. DOI: 10.1159/000322870. View

19.

Zhang F, Shen G, Liu X, Wang F, Zhao H, Yu J . Hypoxic induction of human erythroid-specific δ-aminolevulinate synthase mediated by hypoxia-inducible factor 1. Biochemistry. 2011; 50(7):1194-202. DOI: 10.1021/bi101585c. View

20.

Zhang L, Lau Y, Xi L, Hong R, Kim D, Chen C . Tyrosine kinase inhibitors, emodin and its derivative repress HER-2/neu-induced cellular transformation and metastasis-associated properties. Oncogene. 1998; 16(22):2855-63. DOI: 10.1038/sj.onc.1201813. View