Reversible Modulation of Cell Cycle Kinetics in NIH/3T3 Mouse Fibroblasts by Inducible Overexpression of Mitochondrial Manganese Superoxide Dismutase
- 1 June 2004
- journal article
- research article
- Published by Mary Ann Liebert Inc in Antioxidants and Redox Signaling
- Vol. 6 (3) , 489-500
- https://doi.org/10.1089/152308604773934251
Abstract
To study the mechanism(s) by which manganese-containing superoxide dismutase (MnSOD) mediates cellular growth inhibition, an inducible retroviral vector system regulated by the lac repressor was used to overexpress MnSOD protein in NIH/3T3 cells. Increased MnSOD activity led to decreased cell growth due to prolonged cell cycle transition times in G1 and S phases without significant changes in G2/M phase. Changes in cell cycle transition time were reversible and tightly correlated with MnSOD levels. A transient increase of reactive oxygen species and concomitant decrease in mitochondrial membrane potential were documented following MnSOD induction. N-Acetyl-L-cysteine prevented growth inhibition by MnSOD. Our data suggest that MnSOD may serve a physiological function of regulating cell cycle progression through its prooxidant activity of generating hydrogen peroxide, resulting in coordination of mitochondrial redox state and cellular proliferation.Keywords
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