| First Author | Singh MP | Year | 2017 |
| Journal | Arch Biochem Biophys | Volume | 631 |
| Pages | 42-48 | PubMed ID | 28803836 |
| Mgi Jnum | J:248699 | Mgi Id | MGI:6094915 |
| Doi | 10.1016/j.abb.2017.08.008 | Citation | Singh MP, et al. (2017) Methionine sulfoxide reductase A protects against lipopolysaccharide-induced septic shock via negative regulation of the proinflammatory responses. Arch Biochem Biophys 631:42-48 |
| abstractText | Methionine sulfoxide reductase A (MsrA) is a major antioxidant enzyme that specifically catalyzes the reduction of methionine S-sulfoxide. In this study, we used MsrA gene-knockout (MsrA(-/-)) mice and bone marrow-derived macrophages (BMDMs) to investigate the role of MsrA in the regulation of inflammatory responses induced by lipopolysaccharide (LPS). MsrA(-/-) mice were more susceptible to LPS-induced lethal shock than wild-type (MsrA(+/+)) mice. Serum levels of the proinflammatory cytokines IL-6 and TNF-alpha induced by LPS were higher in MsrA(-/-) than in MsrA(+/+) mice. MsrA deficiency in the BMDMs also increased the LPS-induced cytotoxicity as well as TNF-alpha level. Basal and LPS-induced reactive oxygen species (ROS) levels were higher in MsrA(-/-) than in MsrA(+/+) BMDMs. Phosphorylation levels of p38, JNK, and ERK were higher in MsrA(-/-) than in MsrA(+/+) BMDMs in response to LPS, suggesting that MsrA deficiency increases MAPK activation. Furthermore, MsrA deficiency increased the expression and nuclear translocation of NF-kappaB and the expression of inducible nitric oxide synthase, a target gene of NF-kappaB, in response to LPS. Taken together, our results suggest that MsrA protects against LPS-induced septic shock, and negatively regulates proinflammatory responses via inhibition of the ROS-MAPK-NF-kappaB signaling pathways. |
