ヒトの造血性幹細胞における多剤流出ポンプであるP-グリコプロテインの発現と活性

P M Chaudhary¹, I B Roninson

¹Department of Genetics, University of Illinois, Chicago 60612.

Cell

|July 12, 1991

まとめ

血液形成性幹細胞は,P-glycoprotein (P-gp) 活動によるロダミン123染色が低い. この発見は,骨髄における幹細胞の浄化と化学療法に対する耐性を影響する.

科学分野:

血液学ヘマトロジ
細胞生物学細胞生物学
バイオケミストリーバイオケミストリー

背景:

ロダミン123 (Rh123) のようなミトコンドリアの光染料は,血液形成幹細胞の活動を評価するために使用されます.
Rh123および他の染料は,多剤耐性における重要な流出ポンプであるP-グリコタンパク質 (P-gp) の基板である.

研究の目的:

造血幹細胞におけるP-gp発現と光染料の吸収の関係を調査する.
これらの細胞の観察された低Rh123染色におけるP-gpの役割を明確にするために.

主な方法:

人間の骨髄細胞の染色を光染料で評価する.
P-gp阻害剤を用いて,染料の吸収の変化を観察する.
染料の染色レベルと,血液形成の原始細胞におけるP-gp発現を相関させる.

主要な成果:

人間の骨髄細胞における光染料の染色は,P-gp阻害剤によって強化される.
染料の吸収は,P-gp発現レベルと逆相関しています.
P-gpは,ほとんどの造血原始細胞で発現し,多能幹細胞で最高レベルである.

結論:

低Rh123染色はP-gp流出によるもので,必ずしも低ミトコンドリア活性ではない.
造血幹細胞におけるP-gp発現は,幹細胞の浄化戦略に重大な影響を及ぼします.
P-gpレベルを理解することは,がん化学療法に対する骨髄の抵抗性を改善するために重要です.

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