Role of Peroxiredoxin 2 in the Protection Against Ferrous Sulfate-Induced Oxidative and Inflammatory Injury in PC12 Cells
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Peroxiredoxin 2 (Prdx2) is a ubiquitous antioxidant enzyme in mammalian brain. Although a protective role of Prdx2 has been established in cerebral ischemia and several neurodegenerative diseases, its contribution against iron-induced neurocytotoxicity still remains to be determined. Accordingly, in this study, we aimed to investigate the effects of Prdx2 on iron-induced cytotoxicity using an in vitro model in which PC12 cells are exposed to ferrous sulfate (FS). The FS treatment increased Prdx2 expression, and promoted lactate dehydrogenase (LDH) release and cell apoptosis in PC12 cells, accompanied by the increase in the Bax/Bcl2 ratio, cytochrome c release, and caspase-3 cleavage. FS exposure also increased the malondialdehyde content (lipid peroxidation), 3′-nitrotyrosine expression (protein nitration), γ-H2A.X formation (DNA oxidation), and promoted nuclear factor kappa B nuclear translocation, cyclooxygenase-2 expression, and release of tumor necrosis factor-α and interleukin-1β. Lentivirus-mediated Prdx2 knockdown intensified the FS-induced LDH release and cell apoptosis by aggravating the oxidative and inflammatory damage. In conclusion, our findings demonstrated that Prdx2 played a vital role in the protection against iron-induced cytotoxicity in PC12 cells.
KeywordsPeroxiredoxin 2 Iron toxicity Oxidative stress Inflammatory response Apoptosis
This work was supported by the National Natural Science Foundation of China (81301127 and 81401867), the China Postdoctoral Science Foundation (2014T70661 and 2014M560562) and the Key Research and Development Program of Shandong Province (2015GSF118095).
YL and FL conceived and designed the experiments; WX, ZX, BS and JC performed the experiments; WX and ZX analyzed the data; WX and FL wrote the paper.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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