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KAKEN_24659154seika.pdf
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Download
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:269.1 KB
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:Apr 11, 2016 |
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| Title |
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低酸素センサーPHD2によるCori回路の新規活性化メカニズムの解明
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テイサンソ センサー PHD2 ニ ヨル Cori カイロ ノ シンキ カッセイカ メカニズム ノ カイメイ
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Teisanso sensa PHD2 ni yoru Cori kairo no shinki kasseika mekanizumu no kaimei
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Elucidation of activating Cori cycle caused by inhibition of PHD2 in liver
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笠原, 正貴
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カサハラ, マサタカ
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Kasahara, Masataka
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慶應義塾大学・医学部・講師(非常勤)
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Research team head
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科研費研究者番号 : 30328265
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南嶋, 洋司
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ミナミシマ, ヨウジ
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Minamishima, Yoji
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慶應義塾大学・医学部・講師
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Research team member
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科研費研究者番号 : 20593966
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久保, 亜紀子
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クボ, アキコ
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Kubo, Akiko
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慶應義塾大学・医学部・特任講師
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Research team member
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科研費研究者番号 : 50455573
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菱木, 貴子
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ヒシキ, タカコ
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Hishiki, Takako
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慶應義塾大学・医学部・講師
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Research team member
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科研費研究者番号 : 10338022
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2015
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科学研究費補助金研究成果報告書
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2014
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| Abstract |
酸素濃度が低下した環境下では, 生体のエネルギー代謝は『低酸素モード』に切り替わる。本研究では, 肝細胞特異的に低酸素応答が活性化したマウス(PHD2-LKOマウス)を用いて, 低酸素応答による乳酸代謝の制御メカニズムの解明を試みた。
PHD2-LKOマウスは運動能力, 乳酸処理能力が向上し, 乳酸の細胞内取り込みと代謝が活性化されたことが確認できた。以上から, 肝細胞特異的な低酸素応答を介して乳酸代謝が亢進し, 乳酸クリアランスが高まることがわかった。また, その機序として糖新生経路の活性化が示唆された。
Prolyl hydroxylase 2 (PHD2) is an oxygen sensor that regulate the activity of the hypoxia inducible factors in an oxygen dependent manner. The purpose of this study was to examine whether inactivation of PHD2 in the liver played an important role for activating Cori cycle and decreasing lactate levels in circulation.
Blood lactate levels after treadmill test or lactate tolerance test were significantly lower in PHD2-liver-specific knockout (PHD2-LKO) mice. The stable isotope labeled lactate incorporation assay revealed that livers of PHD2-LKO mice produced significantly greater amounts of glucose derived from the labeled lactate than controls, suggesting that the blockade of PHD2 in the liver helps improve lactic acidosis by activating gluconeogenesis from lactate.
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研究種目 : 挑戦的萌芽研究
研究期間 : 2012～2014
課題番号 : 24659154
研究分野 : 医化学
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