Department of Life Science, Laboratory of Functional Glycomics, Ajou University, San 5, Wonchon-dong, Suwon 443-749, Republic of Korea.
Biochem Biophys Res Commun. 2011 Apr 29;408(1):52-7. doi: 10.1016/j.bbrc.2011.03.115. Epub 2011 Mar 29.
O-linked N-acetylglucosaminyltransferase (OGT)-mediated protein O-GlcNAcylation has been revealing various aspects of functional significance in biological processes, such as cellular signaling and activation of immune system. We found that OGT is maintained as S-nitrosylated form in resting cells, and its denitrosylation is triggered in innate immune response of lipopolysaccharide (LPS)-treated macrophage cells. S-nitrosylation of OGT strongly inhibits its catalytic activity up to more than 80% of native OGT, and denitrosylation of OGT leads to protein hyper-O-GlcNAcylation. Furthermore, blockage of increased protein O-GlcNAcylation results in significant loss of nitric oxide and cytokine production. We propose that denitrosylation of S-nitrosylated OGT is a direct mechanism for upregulation of OGT activity by which immune defense is critically controlled in LPS-stimulated innate immune response.
O-连接 N-乙酰氨基葡萄糖转移酶（OGT）介导的蛋白质 O-GlcNAc ylation 已经揭示了生物过程中各种功能意义，例如细胞信号转导和免疫系统的激活。我们发现，OGT 在静止细胞中保持 S-亚硝酰化形式，并且其脱亚硝化为脂多糖（LPS）处理的巨噬细胞细胞固有免疫反应所触发。OGT 的 S-亚硝酰化强烈抑制其催化活性，高达天然 OGT 的 80％以上，而 OGT 的脱亚硝化为蛋白质超 O-GlcNAc ylation 导致。此外，增加的蛋白质 O-GlcNAcylation 的阻断导致一氧化氮和细胞因子产生的显著损失。我们提出，S-亚硝酰化 OGT 的脱亚硝化为 OGT 活性的上调的直接机制，通过该机制在 LPS 刺激的固有免疫反应中关键地控制免疫防御。
