アポトーシスを誘発する因子によるポリー (((ADP-リボース) ポリメラーゼ-1依存細胞死を媒介する
Seong-Woon Yu1, Hongmin Wang, Marc F Poitras
1Department of Neurology and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Science (New York, N.Y.)
|July 13, 2002
まとめ
ポリー ((ADP-リボース) ポリメラーゼ-1 (PARP-1) は,ミトコンドリアからアポトーシス誘発因子 (AIF) の放出をシグナルすることにより,プログラム細胞死を誘発する. このカスパーゼから独立した経路は,DNA損傷反応と細胞生存に不可欠です.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- ポリー ((ADP-リボース) ポリメラーゼ-1 (PARP-1) は,DNA損傷監視ネットワーク内のゲノム保護に不可欠です.
- また,PARP-1は,イシュケミア・リパーフュージョン損傷,グルタミン酸エキシト毒性,炎症性状態の後の細胞死を媒介する役割も果たしている.
研究 の 目的:
- プログラム細胞死経路におけるPARP-1の役割を明らかにする.
- PARP-1-媒介による細胞死におけるアポトーシス誘発因子 (AIF) の関与を調査する.
主な方法:
- 様々な細胞死誘発剤を用いて,PARP-1の活性化とそのアポトーシス誘発因子 (AIF) 転位に対する効果を調査した.
- 細胞死メカニズムを評価するために,PARP阻害剤とPARP-1の遺伝子ノックアウトを使用しました.
- AIFの機能をブロックするために,抗体マイクロインジェクションを使用した.
主要な成果:
- PARP-1の活性化は,AIFのミトコンドリアから核への転移に不可欠です.
- AIFは,PARP-1に依存した細胞死のために必要であり,カスパースに依存していないことが判明しました.
- PARP阻害剤とPARP-1遺伝子ノックアウトは,AIF転位とそれに続く細胞死を予防しました.
- 抗体でAIFをブロックすることは,PARP-1-依存性細胞毒性から細胞を保護します.
結論:
- PARP-1の活性化により,カスペーゼに依存しないプログラム細胞死経路が開始されます.
- この経路は,AIFがミトコンドリアから放出されるシグナリングを含む.
- PARP-1とAIFは,DNA損傷やその他の細胞毒性攻撃に対する細胞反応の重要な構成要素です.
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