O-Linked β-N-Acetylglucosamine Modification of A20 Enhances the Inhibition of NF-κB (Nuclear Factor-κB) Activation and Elicits Vascular Protection After Acute Endoluminal Arterial Injury

摘要: Objective— Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation a rat model carotid injury by interfering with NF-κB (nuclear factor-κB) signaling. However, the specific molecular target for O-GlcNAcylation is responsible protection remains unclear. In this study, test hypothesis increased A20 required glucosamine-mediated inhibition protection. Approach Results— cultured cells, both glucosamine selective N-acetylglucosaminidase inhibitor thiamet G significantly O-GlcNAcylation. Thiamet treatment did not increase expression but enhance binding to TAX1BP1, key regulatory activity. Adenovirus-mediated overexpression further enhanced effects on prevention TNF-α (tumor necrosis factor-α)–induced IκB degradation, p65 phosphorylation, increases DNA-binding inhibitory TNF-α–induced proinflammatory cytokine cell migration proliferation, whereas silencing endogenous transfection shRNA attenuated these effects. balloon-injured arteries, markedly inhibited activation compared vehicle treatment. Adenoviral delivery injured arteries dramatically reduced balloon injury–induced inflammatory response scramble completely abolished glucosamine. Conclusions— These results suggest plays role negative regulation signaling cascades TNF-α–treated culture acutely thus protecting against inflammation-induced injury.