伊利諾依大學芝加哥分校研究人員在12月9日出版的Cancer Cell上發表特刊文章，講述氧化作用路徑與細胞衰老以及細胞凋亡間的關聯。
文章通訊作者Nissim Hay博士早年在以色列Weizmann研究所獲得博士學位，現任伊利諾依大學芝加哥分校生物化學與分子遺傳學院任教授，主要研究細胞分裂，細胞代謝和癌症的遺傳學變化，主要應用的技術包括，細胞生物學技術，生物化學技術，分子生物學技術和基因敲除技術。
Akt通路是膜受體信號向細胞內轉導的重要途徑，它們調節著細胞凋亡、生長以及一些重要基因的表達。
Akt缺陷會導致對衰老性複製產生耐受作用，對氧化應激或致癌基因Ras誘導的早衰產生耐受作用， 同時還對活性氧簇（reactive oxygen species，ROS）介導的細胞凋亡產生耐受作用。
Akt活化可誘導早衰，並通過增加胞內ROS增加氧耗量和表達ROS清除下遊FoxO尤其是sestrin致敏ROSE介導的細胞凋亡作用。這些結果表明，研究者找到Akt的關鍵弱點，可以逆轉Akt通過多種細胞凋亡刺激因子誘導細胞凋亡的過程。Akt可以停止抑制ROS介導的細胞凋亡。
研究小組還發現，用rapamycin治療癌症可促進激活Akt，抑制etopototic超敏化，促進癌細胞凋亡。單獨使用rapamycin可有選擇性地激活Akt，清除癌細胞。（生物谷Bioon.com）
生物谷推薦原始出處：
Cancer Cell, Volume 14, Issue 6, 458-470, 9 December 2008
Akt Determines Replicative Senescence and Oxidative or Oncogenic Premature Senescence and Sensitizes Cells to Oxidative Apoptosis
Veronique Nogueira1,Youngkyu Park1,Chia-Chen Chen1,Pei-Zhang Xu1,Mei-Ling Chen1,Ivana Tonic1,Terry Unterman2,3andNissim Hay1,,
1 Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA
2 Department of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA
3 Jesse Brown VA Medical Center, Chicago, IL 60612, USA
SUMMARY
Akt deficiency causes resistance to replicative senescence, to oxidative stress- and oncogenic Ras-induced premature senescence, and to reactive oxygen species (ROS)-mediated apoptosis. Akt activation induces premature senescence and sensitizes cells to ROS-mediated apoptosis by increasing intracellular ROS through increased oxygen consumption and by inhibiting the expression of ROS scavengers downstream of FoxO, particularly sestrin 3. This uncovers an Achilles' heel of Akt, since in contrast to its ability to inhibit apoptosis induced by multiple apoptotic stimuli, Akt could not inhibit ROS-mediated apoptosis. Furthermore, treatment with rapamycin that led to further Akt activation and resistance to etoposide hypersensitized cancer cells to ROS-mediated apoptosis. Given that rapamycin alone is mainly cytostatic, this constitutesa strategy for cancer therapy that selectively eradicates cancer cells via Akt activation.