Functional consequences of Peroxiredoxin-5 gene inactivation in the mouse
(2019)
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- Authors
- Supervisors
- Knoops, Bernard
- Abstract
- Peroxiredoxins (Prdxs) are a superfamily of peroxidases widely distributed among prokaryotes and eukaryotes. Prdx5 is ubiquitously expressed in tissues and its role as cytoprotective antioxidant enzyme as well as modulator of redox signaling have been largely reported in vitro. The goal of this work was to study in vivo Prdx5 functions through the generation of transgenic mice in which Prdx5 gene was disrupted using gene trapping strategy. Prdx5 knockout (Prdx5-/-) mice are viable and fertile. The vulnerability of Prdx5-/- mice to lipopolysaccharide (LPS) in vivo was examined. Our results show that Prdx5-/- mice mortality is significantly higher after intraperitoneal injection of 20 mg/kg of LPS compared to the Prdx5+/+. A proteomic analysis of proteins extracted from primary culture of Prdx5-/- and Prdx5+/+ phagocytes, exposed for 24 hours to 1 μg/ml LPS revealed that proteins related to inflammation, cancer, apoptosis and redox state regulation were altered in the Prdx5-/- phagocytes. Also, 41 % of old Prdx5-/- mice developed significantly more tumors compared to 16 % of Prdx5+/+ animals, suggesting that Prdx5 protein is involved in tumor suppression in vivo. Most of the tumors are characterized as lymphoma and hepatocarcinoma. Moreover, the Akt/PTEN signaling pathway in Prdx5-/- MEF cells was investigated, showing that phosphorylation of Akt is higher in Prdx5-/- cells exposed to H2O2. Finally, the consequences of Prdx5 gene inactivation was examined in the central nervous system. Prdx5-/- mice present significantly less motor coordination and a tendency of higher anxiety. Additionally, absence of Prdx5 is linked to glial cell proliferation in hippocampus, suggesting a role in neuroinflammation. Altogether, our results suggest that Prdx5 may play important roles in inflammation and in tumor suppression.
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Citations
Argyropoulou, V. (2019). Functional consequences of Peroxiredoxin-5 gene inactivation in the mouse. https://hdl.handle.net/2078.5/127437