earticle

영어

O-linked N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) is a post translational modification, which is modulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). In the present study, we determined that OGA regulates LPS-driven activation of iNOS/NO. PUGNAc, an inhibitor of OGA, suppress LPS-induced induction of iNOS/NO and the gene expression of proinflammatory mediators, indicating that O-GlcNAcase is important enzyme for LPS-mediated inflammatory response. PUGNAc did not affect the NF-κB O-GlcNAcylation in response to LPS. In addition, PUGNAc alter neither the binding of NF-κB subunits to the iNOS promoter nor the transcriptional activity of NF-κB, suggesting that inhibitory effect of PUGNAc on LPS-induced iNOS expression is not mediated by NF-κB inhibition. Instead, PUGNAc down-regulates increased phosphorylated AKT in response to LPS, suggesting that LPS-mediated AKT activation may be associate with OGA. In conclusion, our data demonstrate that LPS-mediated upregulation of iNOS/NO production via OGA regulation. Further studies should be ensued to define a possible mechanism of AKT on LPS-induced iNOS protein expression through OGA regulation.