Peroxiredoxin 5 overexpression decreases oxidative stress and dopaminergic cell death mediated by paraquat

• Published in: Cells & development 2023-09, Vol.175, p.203860-203860, Article 203860
• Main Authors: Duarte-Jurado, Ana Patricia, Loera-Arias, Maria de Jesus, Saucedo-Cardenas, Odila, Montes de Oca-Luna, Roberto, Rodriguez-Rocha, Humberto, Garcia-Garcia, Aracely
• Format: Article
• Language: English
• Subjects: Animals; Antioxidant enzymes; Cell Death - genetics; Humans; Oxidative Stress; Paraquat; Paraquat - pharmacology; Parkinson's disease; Peroxiredoxins; Peroxiredoxins - genetics; Peroxiredoxins - metabolism; Peroxiredoxins - pharmacology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reactive Oxygen Species - pharmacology
• ISSN: 2667-2901; 2667-2901
• DOI: 10.1016/j.cdev.2023.203860

Peroxiredoxins (Prdxs) are thiol-dependent enzymes that scavenge peroxides. Previously, we found that Prdxs were hyperoxidized in a Parkinson's disease model induced by paraquat (PQ), which led to their inactivation, perpetuating reactive oxygen species (ROS) formation. Herein, we evaluated the redox state of the typical 2-Cys-Prx subgroup. We found that PQ induces ROS compartmentalization in different organelles, reflected by the 2-Cys-Prdx hyperoxidation pattern detected by redox eastern blotting. 2-Cys Prdxs are most vulnerable to hyperoxidation, while atypical 2-Cys Peroxiredoxin 5 (Prdx5) is resistant and is expressed in multiple organelles, such as mitochondria, peroxisomes, and cytoplasm. Therefore, we overexpressed human Prdx5 in the dopaminergic SHSY-5Y cell line using the adenoviral vector Ad-hPrdx5. Prdx5 overexpression was confirmed by western blotting and immunofluorescence (IF) and effectively decreased PQ-mediated mitochondrial and cytoplasmic ROS assessed with a mitochondrial superoxide indicator and DHE through IF or flow cytometry. Decreased ROS mediated by Prdx5 in the main subcellular compartments led to overall cell protection against PQ-induced cell death, which was demonstrated by flow cytometry using Annexin V labeling and 7-AAD. Therefore, Prdx5 is an attractive therapeutic target for PD, as its overexpression protects dopaminergic cells from ROS and death, which warrants further experimental animal studies for its subsequent application in clinical trials. [Display omitted] •Typical 2-Cys Prdxs redox state induced by PQ reflects ROS subcellular compartmentalization•Peroxiredoxin 5 overexpression decreases mitochondrial and cytoplasmic ROS generated by paraquat•Redox homeostasis restoration by Prdx5 overexpression leads to general protection against PQ-induced dopaminergic cell death