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フルクトーゼによる糖分解は,裸のモールラットの無酸素抵抗を支える

Thomas J Park¹, Jane Reznick², Bethany L Peterson³

¹Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA. glewin@mdc-berlin.de tpark@uic.edu.

Science (New York, N.Y.)

|April 22, 2017

まとめ

アフリカのヌードモールラットは果糖代謝に切り替えることで極度の酸素不足を生き延びます裸のモールラット (Heterocephalus glaber) のこのユニークな代謝適応は,ヒトの低酸素損傷を軽減するための洞察を提供します.

科学分野:

動物学
比較生理学
生物化学

背景:

アフリカの裸モールラット (Heterocephalus glaber) は,自然に低酸素の地下環境に住んでいます.
これらの歯類は,長期にわたる低酸素 (低酸素) と完全な酸素不足 (無酸素) に著しい耐性を発揮します.

研究の目的:

裸のモールラットの異常な耐性に対する代謝メカニズムを調べるためだ
重度の酸素欠乏で生存を可能にする分子経路を特定する

主な方法:

裸のモールラットでの無酸素誘導実験
フルクトースの蓄積と代謝を含む代謝経路の分析
主要な代謝酵素とトランスポーター (例えば,GLUT5,ケトヘキソキナーゼ) の遺伝子発現分析

主要な成果:

裸のモールラットは無酸素状態でフルークトーゼで代謝する
フルクトーズは脳で活発に蓄積され,乳酸に代謝されます.
GLUT5 フルクトーストランスポーターとケトヘキソキナーゼのアップレギュレーションは,重要な分子シグネチャーです.
フルクトースの代謝は,フォスフォフルクトキナーゼの阻害を回避し,糖分解と細胞活性をサポートします.

結論:

裸のモールラットは糖分分解の独特な代謝再配線を利用しフルクトースを使って無酸素状態を生き残ります
このフルクトーゼによる代謝戦略は酸素不足の致死的な影響を回避します
このメカニズムの理解は,ヒトの疾患における低酸素状態に対する新しい治療戦略につながる可能性があります.

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