Antioxidant activity is required for the protective effects of cyclophilin A against oxidative stress

Kim,Kiyoon; Oh,In   Kyung; Yoon,Kyung  Sik; Ha,Joohun; Kang,Insug; Choe,Wonchae

doi:10.3892/mmr.2015.3392

Antioxidant activity is required for the protective effects of cyclophilin A against oxidative stress

Authors:
- Kiyoon Kim
- In Kyung Oh
- Kyung Sik Yoon
- Joohun Ha
- Insug Kang
- Wonchae Choe
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Affiliations: Department of Biochemistry and Molecular Biology, Medical Science and Engineering Research Center for Bioreaction to Reactive Oxygen Species, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea
Published online on: February 26, 2015 https://doi.org/10.3892/mmr.2015.3392
Pages: 712-718

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Abstract

Cyclophilin (Cyp) belongs to a group of proteins that have peptidyl‑prolyl cis‑trans isomerase (PPIase) activity. CypA is the major cellular target for the immunosuppressive drug cyclosporin A and mediates its actions. Previous studies have demonstrated that CypA has diverse cellular functions and have suggested that CypA may function as an antioxidant. The present study investigated the antioxidant activity of CypA and its association with PPIase activity. The purified CypA/wild‑type (WT) and CypA/P16S mutant proteins were active in PPIase assays. A total antioxidant capacity assay revealed that the purified CypA/WT protein had significantly higher antioxidant activity, whereas the CypA/P16S mutant was defective in its antioxidant activity. To confirm the importance of CypA antioxidant activity, CypA/P16S was overexpressed in Chang human liver cells and the rate of cell death was measured following treatment with cisplatin or H2O2. Overexpression of CypA/WT protected the cells against cisplatin or H2O2‑induced oxidative damage, however, the CypA/P16S mutant had no effect. These findings suggested that CypA exhibits a protective antioxidant effect.

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