Subscribe to RSS
DOI: 10.1055/a-2672-6959
Die Rolle der H₂O₂-Entgiftung bei oxidativer Stressbelastung der Mitochondrien
Teil 1: Das „SOD2-Paradoxon“Authors

Der Polymorphismus rs4880 im SOD2-Gen beeinflusst die Abwehr von oxidativem Stress in den Mitochondrien, da er für einen verminderten Import des Enzyms in die Mitochondrien und damit einer verminderten Umwandlung von Hyperoxid zu H2O2 prädisponiert. Das Enzym SOD2 schützt zudem nur optimal, wenn das H2O2-abbauende Enzym GPX1 ausreichend vorhanden ist. Ist die GPX1-Aktivität (durch Polymorphismen im GPX1-Gen oder Selenmangel) vermindert, kann – auch bei normaler SOD2-Aktivität – oxidativer Stress durch die verstärkte Bildung von Hydroxylradikalen entstehen („SOD2-Paradoxon“). Eine Abschätzung der Disposition zu verstärktem oxidativem Stress der Mitochondrien sollte Polymorphismen in den SOD2- und GPX1-Genen sowie den Selenstatus betrachten.
Schlüsselwörter
Superoxiddismutase 2 (SOD2) - SOD2-Paradoxon - Glutathionperoxidase 1 (GPX1) - Hyperoxid-Anion - Mitochondrien - Polymorphismus rs4880 - oxidativer StressPublication History
Article published online:
29 September 2025
© 2025. Thieme. All rights reserved.
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
Literatur
- 1 Grujicic J, Allen AR. Manganese Superoxide Dismutase: Structure, Function, and Implications in Human Disease. Antioxidants (Basel) 2025; 14: 848
- 2 Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria Journal of Medicine 2018; 54: 287-293
- 3 Sutton A, Khoury H, Prip-Buus C. et al. The Ala16Val genetic dimorphism modulates the import of human manganese superoxide dismutase into rat liver mitochondria. Pharmacogenetics 2003; 13: 145-157
- 4 Broz M, Furlan V, Lešnik S. et al. The Effect of the Ala16Val Mutation on the Secondary Structure of the Manganese Superoxide Dismutase Mitochondrial Targeting Sequence. Antioxidants (Basel) 2022; 11: 2348
- 5 Bastaki M, Huen K, Manzanillo P. et al. Genotype-activity relationship for Mn-superoxide dismutase, glutathione peroxidase 1 and catalase in humans. Pharmacogenet Genomics 2006; 16: 279-286
- 6 Palma FR, He C, Danes JM. et al. Mitochondrial Superoxide Dismutase: What the Established, the Intriguing, and the Novel Reveal About a Key Cellular Redox Switch. Antioxid Redox Signal 2020; 32: 701-714
- 7 Seitz R, Tümen D, Kunst C. et al. Exploring the Thioredoxin System as a Therapeutic Target in Cancer: Mechanisms and Implications. Antioxidants (Basel) 2024; 13: 1078
- 8 Tian C, Fang S, Du X, Jia C. Association of the C47T polymorphism in SOD2 with diabetes mellitus and diabetic microvascular complications: a meta-analysis. Diabetologia 2011; 54: 803-811
- 9 McKnight AJ, Patterson CC, Mollsten A. et al Review of Genetic Association in the SOD2 Gene with Chronic Kidney Disease: Case-Control Studies and Meta-Analysis Confirm Association with Diabetic Nephropathy. Nephrology Research & Reviews 2012; 4: 51-54
- 10 Pourvali K, Abbasi M, Mottaghi A. Role of Superoxide Dismutase 2 Gene Ala16Val Polymorphism and Total Antioxidant Capacity in Diabetes and its Complications. Avicenna J Med Biotechnol 2016; 8: 48-56
- 11 Sultan S, Alharbi M, Alrayes N. et al. Association of a single nucleotide polymorphism in SOD2 with susceptibility for the development of diabetic nephropathy in patients with type 2 diabetes: A Saudi population study. Endocrinol Diabetes Metab 2023; 6: e449
- 12 Jones DA, Prior SL, Tang TS. et al. Association between the rs4880 superoxide dismutase 2 (C>T) gene variant and coronary heart disease in diabetes mellitus. Diabetes Res Clin Pract 2010; 90: 196-201
- 13 Wang P, Zhu Y, Xi S. et al. Association between MnSOD Val16Ala Polymorphism and Cancer Risk: Evidence from 33,098 Cases and 37,831 Controls. Dis Markers 2018; 2018: 3061974
- 14 Nikic P, Dragicevic D, Jerotic D. et al. Polymorphisms of Antioxidant Enzymes SOD2 (rs4880) and GPX1 (rs1050450) Are Associated with Bladder Cancer Risk or Its Aggressiveness. Medicina (Kaunas) 2023; 59: 131
- 15 Fallah F, Colagar AH, Saleh HA, Ranjbar M. Variation of the genes encoding antioxidant enzymes SOD2 (rs4880), GPX1 (rs1050450), and CAT (rs1001179) and susceptibility to male infertility: a genetic association study and in silico analysis. Environ Sci Pollut Res Int 2023; 30: 86412-86424
- 16 de Oliveira Paludo FJ, de Bittencourt Pasquali MA, de Vargas AR. et al. Influences of the polymorphisms of the Sod2 gene (rs4880) on the motility and vigor of X- and Y-bearing sperm at different pH values. Biomed Pharmacother 2021; 142: 111993
- 17 Halliwell B. Oxidative stress and cancer: have we moved forward?. Biochem J 2007; 401: 1-11
- 18 Kang SW. Superoxide dismutase 2 gene and cancer risk: evidence from an updated meta-analysis. Int J Clin Exp Med 2015; 8: 14647-14655
- 19 Read AD, Bentley RET, Martin AY. et al. Electron Leak From the Mitochondrial Electron Transport Chain Complex I at Site IQ Is Crucial for Oxygen Sensing in Rabbit and Human Ductus Arteriosus. J Am Heart Assoc 2023; 12: e029131
- 20 Seitz R, Tümen D, Kunst C. et al. Exploring the Thioredoxin System as a Therapeutic Target in Cancer: Mechanisms and Implications. Antioxidants (Basel) 2024; 13: 1078
- 21 Shimoda-Matsubayashi S, Matsumine H, Kobayashi T. et al Structural dimorphism in the mitochondrial targeting sequence in the human manganese superoxide dismutase gene. A predictive evidence for conformational change to influence mitochondrial transport and a study of allelic association in Parkinson's disease. Biochem Biophys Res Commun 1996; 226: 561-565 Erratum in: Biochem Biophys Res Commun 1996; 229: 361