title: A high concentration of triiodothyronine attenuates the stimulatory effect on hemin-induced erythroid differentiation of human erythroleukemia K562 cells.
abstract: Although thyroid hormone is a known stimulator of erythropoietic differentiation, severe anemia is sometimes observed in patients with hyperthyroidism and this mechanism is not fully understood. The aim of this study was to investigate the effect of triiodothyronine (T3) on hemin-induced erythropoiesis. Human erythroleukemia K562 cells were used as an erythroid differentiation model. Cell differentiation was induced by hemin and the effect of pre-incubation with T3 (0.1 to 100 nM) was analyzed by measuring the benzidine-positive rate, hemoglobin content, CD71 expression (transferrin receptor), and mRNA expression for transcription factors related to erythropoiesis and thyroid hormone receptors (TRs). Hemin, a promoter of erythroid differentiation, increased the levels of mRNAs for TRα, TRβ, and retinoid X receptor α (RXRα), as well as those for nuclear factor-erythroid 2 (NFE2), GATA-binding protein 1 (GATA1) and GATA-binding protein 2 (GATA2). Lower concentrations of T3 had a stimulatory effect on hemin-induced hemoglobin production (1 and 10 nM), CD71 expression (0.1 nM), and α-globin mRNA expression (1 nM), while a higher concentration of T3 (100 nM) abrogated the stimulatory effect on these parameters. T3 at 100 nM did not affect cell viability and proliferation, suggesting that the abrogation of erythropoiesis enhancement was not due to toxicity. T3 at 100 nM also significantly inhibited expression of GATA2 and RXRα mRNA, compared to 1 nM T3. We conclude that a high concentration of T3 attenuates the classical stimulatory effect on erythropoiesis exerted by a low concentration of T3 in hemin-induced K562 cells.
authors: Department of General Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan.
authors: Mieno
authors: M
authors: Shiraishi
authors: Yoritsuna
authors: Y
authors: Yamamoto
authors: Nobutaka
authors: N
authors: Hirooka
authors: Yasuhiro
authors: Y
authors: Obuchi
authors: Shoichi
authors: S
authors: Tachibana
authors: Makoto
authors: M
authors: Makishima
authors: Yuji
authors: Y
authors: Tanaka
mesh_terms: D000740:Anemia / Q000209:etiology; D004912:Erythrocytes / Q000187:drug effects*; D004920:Erythropoiesis / Q000187:drug effects*; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D015870:Gene Expression / Q000187:drug effects; D006427:Hemin / Q000494:pharmacology*; D006801:Humans; D006980:Hyperthyroidism / Q000150:complications; D020014:K562 Cells; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011988:Receptors, Thyroid Hormone / Q000235:genetics; D047490:Retinoid X Receptor alpha / Q000235:genetics; D014284:Triiodothyronine / Q000008:administration & dosage*
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D050984:NF-E2 Transcription Factor, p45 Subunit; C494692:NFE2 protein, human; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D047490:Retinoid X Receptor alpha; D014284:Triiodothyronine; D006427:Hemin