title: Lower Superoxide Dismutase 2 (SOD2) Protein Content in Mononuclear Cells Is Associated with Better Survival in Patients with Hemodialysis Therapy.
abstract: Mitochondrial superoxide dismutase 2 (SOD2) converts superoxide anions to hydrogen peroxide and oxygen. Human data on SOD2 protein content in chronic kidney disease (CKD) are sparse and mortality data are lacking. We investigated SOD2 protein content in monocytes from patients with hemodialysis therapy (n = 81), CKD stage 1-5 (n = 120), and healthy controls (n = 13) using in-cell Western assays. SOD2 protein decreased from CKD stage 1 until stage 4 whereas it increased again in stage 5 with and without hemodialysis. SOD2 gene expression, analyzed by quantitative real-time PCR, was not significantly different between the groups. Elevating cellular superoxide production reduced SOD2 protein content. This effect was abolished by the superoxide dismutase mimetic Tempol. Using gelelectrophoresis and Western blot we did not detect nitrotyrosine modifications of SOD2 in CKD. Finally, in patients with CKD stage 5 with hemodialysis therapy higher than median SOD2 protein content was associated with higher all-cause mortality. In conclusion, SOD2 protein content declined in CKD until stage 4 while SOD2 gene expression did not. Increased cellular superoxide anion production might affect SOD2 protein content. In advanced CKD (stage 5) SOD2 protein content increased again, but higher than median SOD2 protein content in these patients did not confer a survival benefit.
authors.affiliation: Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: Katharina
authors.identifier: 0000-0002-6047-7404
authors.initials: K
authors.lastname: Krueger
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Jiangsu, Suzhou 215006, China; Institute of Molecular Medicine, Cardiovascular and Renal Research, University of Southern Denmark, 5000 Odense C, Denmark.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department Nephrology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany.
authors.forename: Alexandra
authors.identifier: 0000-0002-2611-0676
authors.initials: A
authors.lastname: Maier
authors.affiliation: Institute of Molecular Medicine, Cardiovascular and Renal Research, University of Southern Denmark, 5000 Odense C, Denmark; Department of Nephrology, Odense University Hospital, 5000 Odense C, Denmark.
authors.forename: Martin
authors.identifier: 0000-0002-0086-0997
authors.initials: M
authors.lastname: Tepel
authors.affiliation: Department of Nephrology, Odense University Hospital, 5000 Odense C, Denmark; Institute of Clinical Research, University of Southern Denmark, 5000 Odense C, Denmark.
authors.forename: Alexandra
authors.identifier: 0000-0002-3100-8692
authors.initials: A
authors.lastname: Scholze
mesh_terms: D016022:Case-Control Studies; D002423:Cause of Death; D003497:Cyclic N-Oxides / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D053208:Kaplan-Meier Estimate; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D006435:Renal Dialysis / Q000009:adverse effects / Q000401:mortality; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000201:enzymology / Q000401:mortality / Q000628:therapy*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000097:blood* / Q000235:genetics; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D000099156:Superoxide Dismutase 2
chemical_list: D003497:Cyclic N-Oxides; D013113:Spin Labels; D013482:Superoxide Dismutase; D013481:Superoxides; D000099156:Superoxide Dismutase 2; C001803:tempol