The role of O-GlcNAc modification in aging-related deterioration of Toll-like receptor signaling in macrophages

O-GlcNAc 修饰在巨噬细胞 Toll 样受体信号老化相关恶化中的作用

• 批准号: 24790593
• 负责人: SHIRATO Ken
• 金额: $ 2.83万
• 依托单位: Waseda University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790593/
• 关键词: 老化; 加齢; マクロファージ; リポ多糖; 炎症; Toll様受容体; シグナル伝達; 翻訳; ヘキソサミン生合成経路; 糖鎖修飾; 老化; 加齢; マクロファージ; リポ多糖; 炎症; Toll様受容体; シグナル伝達; 翻訳; ヘキソサミン生合成経路; 糖鎖修飾

In the present study, to clarify the molecular mechanism of age-related deterioration of macrophage inflammatory responses, lipopolysaccharide (LPS) responsiveness of peritoneal macrophages were compared between 2-month-old and 12-month-old mice. In middle age, the production of pro-inflammatory cytokine in response to LPS was reduced at the protein level but not at the mRNA level. In addition, Toll-like receptor signaling was not affected in middle age. In contrast, the phosphorylation level of eukaryotic initiation factor (eIF)-2alpha was increased in middle age. These results suggest that macrophage inflammatory responses were deteriorated at the post-transcriptional level in middle age, and that the age-related phenomena are associated with the reduction of mRNA translation mediated by increased phosphorylation of eIF-2alpha.

在本研究中，为了阐明巨噬细胞炎症反应的年龄相关恶化的分子机制，比较了2个月大的小鼠和12个月大的小鼠之间腹膜巨噬细胞的脂多糖（LPS）反应性。在中年，响应于LPS的促炎细胞因子的产生在蛋白质水平下降低，但在mRNA水平上却没有降低。此外，在中年不影响Toll样受体信号传导。相比之下，在中年，真核起始因子（EIF）-2alpha的磷酸化水平增加。这些结果表明，巨噬细胞炎症反应在中年的转录后水平下恶化，并且与年龄相关的现象与EIF-2Alpha磷酸化增加介导的mRNA翻译的减少有关。