シスプラチンとヒトのスーパーオキシドディスミュータゼの相互作用

Lucia Banci¹, Ivano Bertini, Olga Blaževitš

¹Magnetic Resonance Center CERM, University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Florence, Italy. banci@cerm.unifi.it

Journal of the American Chemical Society

|April 5, 2012

まとめ

シスプラチンはヒトのスーパーオキシドディスミュータゼ (hSOD1) に結合し,その結合を防止し,既存の塊を溶かす. これはシスプラチンの可能性を示唆しています.

科学分野:

バイオケミストリーバイオケミストリー
神経科学は神経科学である.
薬理学薬理学とは

背景:

アミオトロフィック横筋硬化症 (ALS) は神経変性疾患で,誤った折りたたまれたタンパク質,特にヒトのスーパーオキシドディスミュータゼ (hSOD1) の結合が特徴です.
hSOD1の酸化および非金属化された形態は,集積傾向があり,ALSの病原化に寄与します.

研究の目的:

シスプラチンとヒトのスーパーオキシドディスミュータゼ (hSOD1) の相互作用を調査する.
ALSの特徴であるhSOD1集積を予防し,逆転させるシスプラチンの可能性を評価する.

主な方法:

ディスルファイド酸化アポ形式を含むhSOD1の様々な形態にシスプラチンの結合を研究した.
シスプラチン-hSOD1相互作用の解離定数を決定しました.
脱金属化酸化hSOD1の集積,溶解,およびモノメリゼーションに対するシスプラチンの効果を試験管内および細胞モデルで評価した.

主要な成果:

シスプラチンは,37 ± 3 μMの解離定数でhSOD1の二硫化酸化アポ形式に結合し,特にシステイン111 (Cys111) と相互作用する.
シスプラチンは,hSOD1.1.2のCu(2) -Zn(2) およびZn(2) -Zn(2) 形態にも結合する.
シスプラチンは,脱金属化酸化hSOD1の結合を効果的に阻害し,既存のhSOD1オリゴーマーを in vitroおよび細胞内で溶解します.

結論:

シスプラチンは,アミオトロフィック横筋硬化症 (ALS) の治療用鉛化合物として有意義な可能性を示しています.
hSOD1アグレゲートと相互作用し,それを破壊する能力は,ALS.のための新しい治療戦略を提供します.

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