硒蛋白SelK介导的棕榈酰化对与小胶质细胞吞噬能力相关蛋白表达的影响研究  

Studies on the Effects of Selenoprotein Selk-Mediated Palmitoylation on the Expression of Proteins Related to Phagocytosis of Microglia

作　　者：郭晓萱 黄洪鹏 贾肖艺 陈长兰[1] 

机构地区：[1]辽宁大学药学院,辽宁 沈阳 [2]济宁医学院药学院,山东 日照

出　　处：《药物资讯》2024年第3期176-186,共11页Pharmacy Information

摘　　要：目的:一些研究中发现,硒蛋白SelK主要在小胶质细胞等免疫细胞中大量表达,并能通过与棕榈酰基转移酶ZDHHC6的结合,介导CD36、IP3R、Calnexin、ASAP2等多个蛋白的棕榈酰化,而上述蛋白质均与免疫细胞的吞噬功能相关。为此研究硒蛋白SelK的棕榈酰化是否能够促进上述蛋白的表达对于阐明硒蛋白SelK提高免疫细胞吞噬功能的机制具有特殊意义。方法:对小胶质细胞BV2用硒蛋白SelK过表达/敲减病毒载体进行SelK的过表达/敲减,收集样品后使用实时定量PCR方法测定CD36和Calnaxin mRNA的转录情况,Western blot方法测定目标蛋白的表达变化。结果:硒蛋白SelK的过表达在提高ZDHHC6的表达同时,显著促进CD36(吞噬细胞模式识别受体之一)与Calnexin(参与内质网中Ca2 向线粒体运输的蛋白质之一)的表达和mRNA转录。并且如预期一样SelK的敲减显著降低上述两种蛋白的蛋白质表达和mRNA转录。结论:硒蛋白SelK通过促进CD36和Calnexin蛋白的棕榈酰化,提高吞噬相关蛋白的稳定表达,从而提高免疫细胞的吞噬功能。Objective: Recent studies have found that selenoprotein K (SelK) is mainly expressed in microglia and other immune cells, and can mediate the palmitoylation of CD36, IP3R, Calnexin, ASAP2 and other proteins, which are related to the phagocytosis of immune cells, by binding to palmitoacyltransferase ZDHHC6. Therefore, it is of special significance to study whether the palmitoylation of SelK can promote the expression of the above proteins for elucidating the mechanism of SELK’s enhancement of the phagocytosis of immune cells. Methods: SelK overexpression/knockdown of microglia BV2 was performed with SelK overexpression/knockdown virus vectors. After collecting samples, real-time quantitative PCR was used to determine the transcription of CD36 and Calnexin mRNA, and Western blot was used to determine the expression of the target proteins. Results: Overexpression of SelK increased the expression of ZDHHC6, and significantly promoted the protein expression and mRNA transcription of Calnexin, one of the phagocyte pattern recognition receptors, and CD36, one of the proteins involved in promoting Ca2 transporting from endoplasmic reticulum to mitochondria, in microglia. As expected, SelK knockdown significantly reduced the protein expression and mRNA transcription of the two proteins. Conclusion: SelK can promote the palmitoylation of CD36 and Calnexin proteins, improve the stable expression of phagocytic related proteins, and thus enhance the phagocytic function of immune cells.

关 键 词：硒蛋白 小胶质细胞 棕榈酰化 吞噬 

分 类 号：R73[医药卫生—肿瘤]