伊利诺依大学芝加哥分校研究人员在12月9日出版的Cancer Cell上发表特刊文章，讲述氧化作用路径与细胞衰老以及细胞凋亡间的关联。
文章通讯作者Nissim Hay博士早年在以色列Weizmann研究所获得博士学位，现任伊利诺依大学芝加哥分校生物化学与分子遗传学院任教授，主要研究细胞分裂，细胞代谢和癌症的遗传学变化，主要应用的技术包括，细胞生物学技术，生物化学技术，分子生物学技术和基因敲除技术。
Akt通路是膜受体信号向细胞内转导的重要途径，它们调节着细胞凋亡、生长以及一些重要基因的表达。
Akt缺陷会导致对衰老性复制产生耐受作用，对氧化应激或致癌基因Ras诱导的早衰产生耐受作用， 同时还对活性氧簇（reactive oxygen species，ROS）介导的细胞凋亡产生耐受作用。
Akt活化可诱导早衰，并通过增加胞内ROS增加氧耗量和表达ROS清除下游FoxO尤其是sestrin致敏ROSE介导的细胞凋亡作用。这些结果表明，研究者找到Akt的关键弱点，可以逆转Akt通过多种细胞凋亡刺激因子诱导细胞凋亡的过程。Akt可以停止抑制ROS介导的细胞凋亡。
研究小组还发现，用rapamycin治疗癌症可促进激活Akt，抑制etopototic超敏化，促进癌细胞凋亡。单独使用rapamycin可有选择性地激活Akt，清除癌细胞。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
