演題詳細

一般口演 / Oral Session

一般口演 1 (Oral Session 1) :鉄代謝 (Iron Metabolism)

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日程
2013年10月11日(金)
時間
09:30 - 10:30
会場
第3会場 / Room No.3 (さっぽろ芸文館 3F 蓬莱)
座長・司会
川端 浩 (Hiroshi Kawabata):1
1:京都大学 血液・腫瘍内科学
 
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Iron deficient anemia involves reconfiguration of erythropoiesis by heme receptor Bach1

演題番号 : OS-1-2

小林 匡洋 (Masahiro Kobayashi):1,2、武藤 哲彦 (Akihiko Muto):2、伊藤 亜里 (Ari Ito):2、藤原 亨 (Toru Fujiwara):1、張替 秀郎 (Hideo Harigae):1、五十嵐 和彦 (Kazuhiko Igarashi):2

1:Department of Rheumatology and Hematology, Tohoku Univ., Japan、2:Department of Biochemistry, Tohoku Univ., Japan

 

Developing erythroid cells must synthesize right amounts of globin proteins and heme because of their intrinsic toxicities. In iron deficient anemia (IDA), coordination of globin and heme syntheses in erythroid cells must be critical. BTB and CNC homology1 (Bach1) is a heme-binding transcriptional repressor and binds to the β-globin locus control region and the enhancer regions of Hmox1 coding heme oxygenase-1 (HO-1). In vitro studies have shown that heme binds to Bach1 to inhibit its DNA binding, achieving derepression of Bach1 target genes. Unexpectedly, Bach1-deficient mice did not exhibit defects in erythropoiesis. In contrast, we found aggravation of IDA in Bach1-deficient mice. Massive aggregates presumably reflecting denatured globin were observed in peripheral red blood cells under IDA in Bach1-deficient mice. While expression of both HO-1 and globin genes was repressed in wild-type erythroid cells upon iron depletion, their expression was high in Bach1-deficient erythroblasts. Bach1 is specifically required for reconfiguration of erythroid differentiation in IDA. We propose a model, referred to as "hemoglobin regulon". In iron deficient erythroid cells, heme concentration is decreased, leading to the activation of Bach1 and thereby an inhibition of globin gene transcription. The expression of HO-1 is also kept low in iron deficient erythroid cells, precluding degradation of heme. Therefore, both heme and globin are maintained to similar levels by Bach1. IDA is not a mere result of iron shortage but is based on an adaptive gene response within erythroid cells.

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