| First Author | Shibuya S | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 7 | PubMed ID | 33805516 |
| Mgi Jnum | J:336604 | Mgi Id | MGI:6751121 |
| Doi | 10.3390/ijms22073542 | Citation | Shibuya S, et al. (2021) Xanthine Oxidoreductase-Mediated Superoxide Production Is Not Involved in the Age-Related Pathologies in Sod1-Deficient Mice. Int J Mol Sci 22(7) |
| abstractText | Reactive oxygen species (ROS) metabolism is regulated by the oxygen-mediated enzyme reaction and antioxidant mechanism within cells under physiological conditions. Xanthine oxidoreductase (XOR) exhibits two inter-convertible forms (xanthine oxidase (XO) and xanthine dehydrogenase (XDH)), depending on the substrates. XO uses oxygen as a substrate and generates superoxide (O2(*-)) in the catalytic pathway of hypoxanthine. We previously showed that superoxide dismutase 1 (SOD1) loss induced various aging-like pathologies via oxidative damage due to the accumulation of O2(*-) in mice. However, the pathological contribution of XO-derived O2(*-) production to aging-like tissue damage induced by SOD1 loss remains unclear. To investigate the pathological significance of O2(*-) derived from XOR in Sod1(-/-) mice, we generated Sod1-null and XO-type- or XDH-type-knock-in (KI) double-mutant mice. Neither XO-type- nor XDH-type KI mutants altered aging-like phenotypes, such as anemia, fatty liver, muscle atrophy, and bone loss, in Sod1(-/-) mice. Furthermore, allopurinol, an XO inhibitor, or apocynin, a nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor, failed to improve aging-like tissue degeneration and ROS accumulation in Sod1(-/-) mice. These results showed that XOR-mediated O2(*-) production is relatively uninvolved in the age-related pathologies in Sod1(-/-) mice. |
