Antioxidant activity is required for the protective effects of cyclophilin A against oxidative stress.
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.
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.
Kiyoon
K
Kim
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.
In Kyung
IK
Oh
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.
Kyung Sik
KS
Yoon
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.
Joohun
J
Ha
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.
Insug
I
Kang
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.
Wonchae
W
Choe
D000975:Antioxidants / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage; D021984:Cyclophilin A / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008099:Liver / Q000166:cytology / Q000378:metabolism; D027361:Organic Anion Transporters / Q000096:biosynthesis / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D019696:Peptidylprolyl Isomerase / Q000096:biosynthesis* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics
D000975:Antioxidants; D002945:Cisplatin; D021984:Cyclophilin A; D006861:Hydrogen Peroxide; D007166:Immunosuppressive Agents; D027361:Organic Anion Transporters; D019696:Peptidylprolyl Isomerase; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; C487009:SLCO6A1 protein, human