Redox stress regulates cell proliferation and apoptosis of human hepatoma through Akt protein phosphorylation

FEBS Letters

Shan-Lin, Liu²  Lian, Wei²  Dong-Yun, Shi²  Ya-Dong, Zhang²  Yu-Ru, Deng¹ 

[1] Department of Physiology, National University of Singapore, Singapore 119260;Department of Biochemistry, Shanghai Medical College of Fudan University, Free Radical Regulation Research Center of Fudan University, Shanghai 200032, PR China

关键词: Redox state;    Akt phosphorylation;    Antioxidant;    Apoptosis;    Electron spin resonance;    Reactive oxygen species;    ROS;    reactive oxygen species;    SM;    Salvia miltriorrhiza;    DPI;    diphenylene iodonium;    PKB;    protein kinase B;    ESR;    electron spin resonance;    NAC;    N-acetyl L-cysteine;    DMPO;    5;    5-dimethyl-1-pyrroline-N-oxide;    SOD;    superoxide dismutase;    PI3K;    phosphatidylinositol 3-kinase;    DCF-DA;    dichlorodihydrofluorescein diacetate;   

DOI  :  10.1016/S0014-5793(03)00338-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Employing a spin trapping agent combined with electron spin resonance spectroscopy, we were able to capture reactive oxygen species (ROS) in living hepatoma cells and first found that the trapped ROS was superoxide anion (O₂ ⁻). O₂ ⁻ suppressed by treatment with diphenylene iodonium, a flavoprotein inhibitor, was generated by the flavoprotein-containing NADPH-oxidase complex. Applying endogenous/exogenous pro-oxidant or antioxidant causes different redox states in hepatoma cells. Akt activity and cell growth were significantly stimulated by treating hepatoma cells with low concentration of ROS, which could be abolished by adding antioxidants. The phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (0.15 μM) inhibited Akt phosphorylation induced by ROS. Our results indicate that hepatoma cell growth is ROS-dependent, and fluctuation of the intracellular redox state may regulate hepatoma cell growth through Akt phosphorylation and the PI3K/Akt pathway, resulting in a broad array of responses from cellular proliferation to apoptosis.

【 授权许可】

Unknown