Dose-dependant regulation of ROS on cell proliferation, apoptosis and necrosis

抄録

Accumulating evidence demonstrate that hydrogen peroxide (H₂O₂) plays essential function in physiological signaling pathways including growth, proliferation, differentiation, migration, and apoptosis. The dosage, localization, and/or activities of cellular antioxidants are important in determining biological responses initiated by H₂O₂. In spite of the fact that low dose (from 0.1µM to 100µM) of H₂O₂ is required in maintaining the normal metabolism, more specific dosages of them still induce different effects including: (1) under physiological condition, high dose of H₂O₂ protects against injury and to clean xenobiotics in cells and tissues; (2) moderate dose of H₂O₂ maintains cell cycle progression through regulation of many signaling pathways; (3) in some cases, H₂O₂ is also needed to initiate antioxidative enzymes, such as manganese superoxide dismutase (MnSOD) and catalase (CAT), by activating NF-E2-related factor2 (Nrf2), and to stimulate proliferation and differentiation of cells in early stage of embryonic development, injury repairment and tumour progressing. H₂O₂ is involved in various redox-regulated processes and controlled by “multi-antioxidats chain” or “antioxidative enzymes chain”. In this study, we found the down-regulation of H₂O₂ level in hepatocytes undergoes a transition from proliferation to cell cycle arrest during development. The higher and steady level of H₂O₂ is required for maintaining cell proliferative status. Intracellular H₂O₂ plays an active role in control of liver cell growth and liver development. These results challenge the traditional view which considers liver H₂O₂ as a solely deleterious byproduct and may pave the way for redox control in the therapy of liver diseases.