Inhibition of cell growth in NIH/3T3 fibroblasts by overexpression of manganese superoxide dismutase: Mechanistic studies
- 1 June 1998
- journal article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 175 (3), 359-369
- https://doi.org/10.1002/(sici)1097-4652(199806)175:3<359::aid-jcp14>3.0.co;2-0
Abstract
NIH/3T3 mouse fibroblasts were transfected with the cDNA for manganese superoxide dismutase (MnSOD), and two clones overexpressing MnSOD activity were subsequently characterized by comparison with parental and control plasmid‐transfected cells. One clone with a 1.8‐fold increase in MnSOD activity had a 1.5‐fold increase in glutathione peroxidase (GPX) activity (increased GPX‐adapted clone), while a second clone with a 3‐fold increase in MnSOD activity had a 2‐fold decrease in copper, zinc superoxide dismutase (CuZnSOD) activity (decreased CuZnSOD‐adapted clone). Increased reactive oxygen species (ROS) levels compared with parental or control plasmid‐transfected cells were observed in nonsynchronous cells in the increased GPX‐adapted clone, but not in the decreased CuZnSOD‐adapted clone. The two MnSOD‐overexpressing clones showed different sensitivities to agents that generate oxidative stress. Flow cytometry analysis of the cell cycle showed altered cell cycle progression in both MnSOD‐overexpressing clones. During logarithmic growth, both MnSOD‐overexpressing clones showed increased mitochondrial membrane potential compared with parental and control plasmid‐transfected cells. Both MnSOD‐overexpressing clones showed a decrease in mitochondrial mass at the postconfluent phase of growth, suggesting that mitochondrial mass may be regulated by MnSOD and/or ROS levels. Our results indicate that adaptation of fibroblasts to overexpression of MnSOD can involve more than one mechanism, with the resultant cell phenotype dependent on the adaptation mechanism utilized by the cell. J. Cell. Physiol. 175:359–369, 1998.Keywords
This publication has 40 references indexed in Scilit:
- Redox modulation of tyrosine phosphorylation-dependent signal transduction pathwaysFree Radical Biology & Medicine, 1996
- Elevation in the Ratio of Cu/Zn-Superoxide Dismutase to Glutathione Peroxidase Activity Induces Features of Cellular Senescence and This Effect Is Mediated by Hydrogen PeroxideHuman Molecular Genetics, 1996
- The Use of RT-PCR to Distinguish between Plasmid MnSOD Transcripts and Endogenous MnSOD mRNABiochemical and Biophysical Research Communications, 1995
- Low-Level Oxidative Stress Causes Cell Cycle-Specific Arrest in Cultured CellsBiochemical and Biophysical Research Communications, 1995
- Oxidants in mitochondria: from physiology to diseasesBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1995
- Mechanisms of cell injury by activated oxygen species.Environmental Health Perspectives, 1994
- A cellular model of oxidant-mediated neuronal injuryBrain Research, 1993
- Overproduction of human Mn‐superoxide dismutase modulates paraquat‐mediated toxicity in mammalian cellsFEBS Letters, 1991
- Isolation and characterization of complementary DNAs encoding human manganese‐containing superoxide dismutaseFEBS Letters, 1988
- Glutathione peroxidase activity in selenium-deficient rat liverBiochemical and Biophysical Research Communications, 1976