| First Author | Lai L | Year | 2019 |
| Journal | Free Radic Biol Med | Volume | 145 |
| Pages | 374-384 | PubMed ID | 31606431 |
| Mgi Jnum | J:287223 | Mgi Id | MGI:6391821 |
| Doi | 10.1016/j.freeradbiomed.2019.10.006 | Citation | Lai L, et al. (2019) Loss of methionine sulfoxide reductases increases resistance to oxidative stress. Free Radic Biol Med 145:374-384 |
| abstractText | Oxidation of methionine residues to methionine sulfoxide scavenges reactive species, thus protecting against oxidative stress. Reduction of the sulfoxide back to methionine by methionine sulfoxide reductases creates a cycle with catalytic efficiency. Protection by the methionine sulfoxide reductases is well documented in cultured cells, from microorganisms to mammals. However, knocking out one or two of the 4 mammalian reductases had little effect in mice that were not stressed. We hypothesized that the minimal effect is due to redundancy provided by the 4 reductases. We tested the hypothesis by creating a transgenic mouse line lacking all 4 reductases and predicted that this mouse would be exceptionally sensitive to oxidative stress. The mutant mice were phenotypically normal at birth, exhibited normal post-natal growth, and were fertile. Surprisingly, rather than being more sensitive to oxidative stress, they were more resistant to both cardiac ischemia-reperfusion injury and to parenteral paraquat, a redox-cycling agent. Resistance was not a result of hormetic induction of the antioxidant transcription factor Nrf2 nor activation of Akt. The mechanism of protection may be novel. |
