| First Author | Singh MP | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 484 |
| Issue | 1 | Pages | 189-194 |
| PubMed ID | 28104395 | Mgi Jnum | J:251527 |
| Mgi Id | MGI:6101658 | Doi | 10.1016/j.bbrc.2017.01.025 |
| Citation | Singh MP, et al. (2017) Methionine sulfoxide reductase A deficiency exacerbates acute liver injury induced by acetaminophen. Biochem Biophys Res Commun 484(1):189-194 |
| abstractText | Acetaminophen (APAP) overdose induces acute liver injury via enhanced oxidative stress and glutathione (GSH) depletion. Methionine sulfoxide reductase A (MsrA) acts as a reactive oxygen species scavenger by catalyzing the cyclic reduction of methionine-S-sulfoxide. Herein, we investigated the protective role of MsrA against APAP-induced liver damage using MsrA gene-deleted mice (MsrA(-/-)). We found that MsrA(-/-) mice were more susceptible to APAP-induced acute liver injury than wild-type mice (MsrA(+/+)). The central lobule area of the MsrA(-/-) liver was more impaired with necrotic lesions. Serum alanine transaminase, aspartate transaminase, and lactate dehydrogenase levels were significantly higher in MsrA(-/-) than in MsrA(+/+) mice after APAP challenge. Deletion of MsrA enhanced APAP-induced hepatic GSH depletion and oxidative stress, leading to increased susceptibility to APAP-induced liver injury in MsrA-deficient mice. APAP challenge increased Nrf2 activation more profoundly in MsrA(-/-) than in MsrA(+/+) livers. Expression and nuclear accumulation of Nrf2 and its target gene expression were significantly elevated in MsrA(-/-) than in MsrA(+/+) livers after APAP challenge. Taken together, our results demonstrate that MsrA protects the liver from APAP-induced toxicity. The data provided herein constitute the first in vivo evidence of the involvement of MsrA in hepatic function under APAP challenge. |
