Natori Yujin, Nasui Miwako, Edo Kiyoto, Sato Shogo, Sakurai Takuya, Kizaki Takako, Kihara-Negishi Fumiko
Department of Life and Health Sciences, School of Pharma-Sciences, Teikyo University.
Department of Research Center for Practical Training of Student Pharmacists, School of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
J Biochem. 2017 Aug 1;162(2):137-143. doi: 10.1093/jb/mvx006.
A sialidase NEU1 that removes sialic acids from glycoconjugates has been implicated in diverse cellular functions. Aberrant NEU1 activity is associated with various pathologies including lysosomal storage disorder sialidosis, autoimmune diseases and the malignancy and metastasis of cancer cells. We recently reported that NEU1 activity increases during 3T3-L1 adipogenesis and that it is higher in the epididymal fat of obese and diabetic mice. However, the precise functions of NEU1 in adipocytes have not been elucidated. Knockdown of NEU1 using siRNA transfection in 3T3-L1 adipocytes significantly decreased the mRNA expression and protein secretion of IL-6 and MCP-1 induced by LPS. The promoter activities of both IL-6 and MCP-1 as well as nuclear factor-kappa B (NF-κB) nuclear translocation were reduced in adipocytes transfected with an siRNA sequence that targets NEU1(siNEU1). NEU1 suppression using siNEU1 affected TLR4 sialylation. These findings suggest that NEU1 is involved in the production of IL-6 and MCP-1 in adipocytes possibly through TLR4/NF-κB signalling.
一种能从糖缀合物中去除唾液酸的唾液酸酶NEU1与多种细胞功能有关。NEU1活性异常与多种病理状况相关，包括溶酶体贮积症唾液酸沉积症、自身免疫性疾病以及癌细胞的恶性增殖和转移。我们最近报道，在3T3-L1脂肪生成过程中NEU1活性增加，且在肥胖和糖尿病小鼠的附睾脂肪中更高。然而，NEU1在脂肪细胞中的具体功能尚未阐明。在3T3-L1脂肪细胞中使用siRNA转染敲低NEU1，显著降低了LPS诱导的IL-6和MCP-1的mRNA表达和蛋白分泌。在用靶向NEU1的siRNA序列（siNEU1）转染的脂肪细胞中，IL-6和MCP-1的启动子活性以及核因子κB（NF-κB）的核转位均降低。使用siNEU1抑制NEU1会影响TLR4的唾液酸化。这些发现表明，NEU1可能通过TLR4/NF-κB信号通路参与脂肪细胞中IL-6和MCP-1的产生。
