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KAKEN_23570172seika.pdf
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Title |
Title |
新規ヘム標的タンパク質HSP27の細胞防御制御機構の解明
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Kana |
シンキ ヘム ヒョウテキ タンパクシツ HSP27 ノ サイボウ ボウギョ セイギョ キコウ ノ カイメイ
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Shinki hemu hyoteki tanpakushitsu HSP27 no saibo bogyo seigyo kiko no kaimei
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Analysis of erythroid differentiation by HSP27
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加部, 泰明
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カベ, ヤスアキ
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Kabe, Yasuaki
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慶應義塾大学・医学部・講師
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Research team head
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科研費研究者番号 : 20397037
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石森, 浩一郎
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イシモリ, コウイチロウ
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Ishimori, Koichiro
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北海道大学・理学部・教授
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Research team member
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科研費研究者番号 : 20192487
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2014
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科学研究費補助金研究成果報告書
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2013
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Abstract |
ヘムは赤血球分化の過程で細胞内に数mMも蓄積されるが、このヘム毒性の回避機構は不明であった。我々は独自のアフィニティ精製技術を応用して、新規ヘム結合タンパク質としてHSP27を同定した。ヘムはHSP27と結合してその多量体構造を直接解離させて活性化してアポトーシス誘導を阻害することを見出した。さらに、HSP27の発現を薬剤誘導性に抑制出来るHSP27ノックダウンマウスの解析により、赤血球形成が始まるE13頃のマウス発生の時期に、HSP27ノックダウン特異的に胎生致死となる事が明らかとなった。また、成熟マウスにおいても赤血球分化能が著しく減少し、異常な形態の幹細胞の蓄積が多く認められた。
During erythropoiesis, haem synthesis is significantly induced, and abundant haem is utilized as hemoglobin in erythroid cells. However, excessive haem results in cell damages by membrane oxidation. In the present study, we found that haem directly bound to heat shock protein 27 (HSP27) by affinity purification. HSP27 is a small heat shock family protein, which plays an important role for cytoprotection, stress tolerance, cellular differentiation or tissue development. It has been known that the multimerized HSP27 dissociates by several stimuli. Interestingly, exposure of haem directly dissociated the multimerized HSP27 in vivo and in vitro. Knockdown of HSP27 expression resulted in the haem-induced apoptosis and reduced the haemin-induced erythroid differentiation. Furthermore, we also found that HSP27 is essential for erythroid differentiation by using HSP27 knockdown mice.
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研究種目 : 基盤研究(C)
研究期間 : 2011~2013
課題番号 : 23570172
研究分野 : 生物学
科研費の分科・細目 : 生物化学・機能生物学
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