活性酸素のp38MAPKを介する造血幹細胞寿命制御

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  • ジュショウ キネン コウザ サンシカイ ショウレイショウ カッセイ サンソ ノ p38MAPK オ カイスル ゾウケツ カンサイボウ ジュミョウ セイギョ
  • カッセイ サンソ ノ p38MAPK オ カイスル ゾウケツ カンサイボウ ジュミョウ セイギョ
  • kassei sanso no p38MAPK o kaisuru zoketsu kansaibo jumyo seigyo

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Hematopoie1ic stem cells(HSCs)are able to self-renew and to differentiate along all hematopoietic lineagesthroughout the entire life-timc of organlsm. Appropriate control of HSC self-renewal is crucial for the mainte-nance of hematopoietic homeostasis. Here we show that activation of p38MAPK in response to increasing!evels of reactive oxygen species (ROS) Iimits the lifespan of HSCs in vivo, In Atm (-/-) mice, elevation of ROSlevels induces HSC-specific phosphorylation of p38MAPK accompanied by a defect in the maintenance of HSCquiescence. lnhibition of p38MAPK rescued ROS-induced defects in HSC repopulating capacity and in themaintenance of HSC quiescence, indicating that the ROS-p38MAPK pathway contributes to exhaustion of thestem cell population. Furthermore, prolonged treatment with an antioxidant or an inhibitor of p38MAPK ex・tended the lifespan of HSCs from wild・type mice in serial transplantation experiments. These data show thatinactivation of p38MAPK protects HSCs against loss of self-rcnewal capacity.

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収録刊行物

  • 慶應医学

    慶應医学 84 (3), 165-168, 2007-09

    慶應医学会

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