期刊
GLYCOCONJUGATE JOURNAL
卷 32, 期 9, 页码 685-693出版社
SPRINGER
DOI: 10.1007/s10719-015-9619-1
关键词
TNF alpha; TNFR1; N-glycosylation; Microglia activation; NF-kappa B
资金
- National Basic Research Program of China (973 Program) [2012CB822104]
- National Natural Science Foundation of China [31500647, 81371299, 31440037, 31270802]
- Natural Science Foundation of the Jiangsu Higher Education Institutions of China [15KJA310003]
- Natural Science Foundation of Jiangsu Province [BK20150408]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
Accumulating evidences demonstrated that microglia activation and the autocrine loop of tumor necrosis factor-alpha (TNF alpha) greatly contribute to the pathogenesis of several CNS diseases. TNF alpha exerts its biological effects by interacting with two different receptors: TNF receptor 1 (TNFR1) and TNFR2. The classic proinflammatory activity of TNF alpha is mainly mediated by TNFR1. In the present study, we found that TNFR1 was modificated by N-glycosylation on Asn151 and Asn202 in microglia. The N-glycosylation of TNFR1 could facilitate its capability of binding to TNF alpha and further promote the formation of TNF alpha autocrine loop in microglia stimulated by TNF alpha, resulting in excessive microglia activation and CNS inflammation. All these processes were related to TNFR1-mediated NF-kappa B pathways. Elimination of N-glycosylation did not affect the subcellular transportation and cell surface localization of TNFR1, but suppressed ligand-binding affinity. These findings indicated that the N-glycosylation of TNFR1 played an important role during microglia activation in CNS inflammation. By this study, we aimed to provide some valuable experimental evidence for a better understanding of the significance of protein glycosylation in microglia inflammatory activation and CNS disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据