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Redox stress regulates cell proliferation and apoptosis of human hepatoma through Akt protein phosphorylation
Author(s) -
Dong-Yun Shi,
Yu-Ru Deng,
Shan-Lin Liu,
Ya-Dong Zhang,
Lian Wei
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00338-7
Subject(s) - phosphorylation , protein kinase b , apoptosis , microbiology and biotechnology , cell growth , redox , chemistry , pi3k/akt/mtor pathway , cancer research , biochemistry , biology , organic chemistry
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 (O 2 − ). O 2 − 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.