Genoprotective and cytoprotective functions of human peroxiredoxin 5
(2005)
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- Authors
- Supervisors
- Knoops, Bernard
- Abstract
- Peroxiredoxin 5 (PRDX5) is a mammalian thioredoxin peroxidase ubiquitously expressed in tissues. PRDX5 can be intracellularly localized to mitochondria, peroxisomes, the cytosol, and, to a lesser extent, the nucleus. This remarkably wide subcellular distribution compared with the five other mammalian PRDXs prompted us to further investigate the antioxidant protective function of PRDX5 according to its subcellular localization. Chinese hamster ovary (CHO) cells overexpressing human PRDX5 in different subcellular compartments were established by stable transfection. The subcellular localization of PRDX5 as well as its level of expression were determined in these CHO clones. We also studied the effects of PRDX5 overexpression on other antioxidant enzymes and showed that PRDX5 overexpression in the cytosol caused an increase in catalase and glutathione peroxidase activities, suggesting that PRDX5 may protect these other antioxidant enzymes against oxidative inactivation, enhancing the overall cellular antioxidant capacity. To evaluate the cytoprotective effects of PRDX5, the CHO clones overexpressing PRDX5 were exposed to different concentrations of hydrogen peroxide or tert-butylhydroperoxide (tBHP), during one hour. In these conditions, high levels of PRDX5 in either the cytosolic, mitochondrial, or nuclear compartment significantly reduced cell death. The mitochondrial PRDX5 overexpression was the most effective, suggesting that PRDX5 exerts an important antioxidant function in this compartment. CHO clones overexpressing PRDX5 were also submitted to long-term exposure with the same peroxides, in absence of serum, to further study the cytoprotective effects of PRDX5. While PRDX5 overexpression conferred higher cell survival in the presence of hydrogen peroxide, it sensitized cells in the presence of tBHP. The functional significance of nuclear PRDX5 is not yet understood. Here, we speculated that PRDX5 can exert an antioxidant function in the nucleus. Using our CHO clones overexpressing PRDX5, we have shown that PRDX5 can act as an alkyl hydroperoxide reductase in the nucleus and thereby protects DNA against oxidative attacks when present at high concentrations in the nucleus. To complete the study of its genoprotective abilities, we demonstrated the protective effects of human recombinant PRDX5 against plasmid DNA damages induced by metal-catalyzed generation of reactive oxygen species. The genoprotective effects of PRDX5 on mitochondrial DNA were also examined using CHO cells that overexpress mitochondrial PRDX5. In these cells, exogenously added hydrogen peroxide caused less mitochondrial DNA damages than in controls cells, suggesting that PRDX5 could play an important role in mitochondrial genome stability. In conclusion, this work provided evidence that overexpression of PRDX5 leads to a gain of cytoprotective function for this thioredoxin peroxidase in mammalian cells. PRDX5, when highly expressed, can exert cyto- as well as genoprotective effects during different range of oxidative stress, reinforcing its role as cytoprotective antioxidant enzyme.
- Affiliations
Citations
Banmeyer, I. (2005). Genoprotective and cytoprotective functions of human peroxiredoxin 5. https://hdl.handle.net/2078.5/124149