安徽大学学报（自然科学版）2025，Vol.49Issue(2)：84-90,7.DOI:10.3969/j.issn.1000-2162.2025.02.010
华法林抑制蛋白C的γ-羧基化致其滞留于内质网
Warfarin inhibiting γ-carboxylation of protein C and retaining it in the endoplasmic reticulum
摘要
Abstract
Warfarin is a commonly used clinical anticoagulant,and some studies have shown that Warfarin can inhibit protein C(PROC)secretion,but the mechanism is unclear.In this paper,to investigate the mechanism underlying the reduced secretion of PROC caused by warfarin,the authors employed an enzyme-linked immunosorbent assay(ELISA)to measure the levels of PROC antigen secretion;the expression of PROC and the level of γ-carboxylation in intracellular and culture medium supernatants were detected by immunoblotting assay;and the subcellular localization of PROC in the cell was analyzed by fluorescence imaging as well as fluorescence quantification.The results showed that Warfarin inhibited PROC total antigen secretion with a concentration-dependent effect.Immunoblot experiments analyzed the levels of PROC within cells and its secretion outside the cells,as well as the γ-carboxylation levels.The findings revealed that a decrease in theγ-carboxylation level of intracellular PROC was associated with a reduction in the secretion of PROC antigen.By cellular sublocalization and quantitative fluorescence analysis,it was found that Warfarin-treated PROC would be retained in the endoplasmic reticulum and could not be transferred to the Golgi apparatus normally;this result also suggested that the y-carboxylation modification of the Gla structural domain of PROC was a key factor affecting its secretion.In conclusion,the above studies suggested that Warfarin affects theγ-carboxylation of the Gla domain of PROC,leading to its retention in the endoplasmic reticulum and inhibiting its secretion.关键词
华法林/蛋白C/γ-羧基化/内质网/维生素K循环/分泌Key words
Warfarin/protein C/γ-carboxylation/endoplasmic reticulum/vitamin K cycle/secretion分类
生物学引用本文复制引用
李晓明,沈滟,曹青,沈国民..华法林抑制蛋白C的γ-羧基化致其滞留于内质网[J].安徽大学学报（自然科学版）,2025,49(2):84-90,7.基金项目
国家自然科学基金资助项目(81770140,82170133) （81770140,82170133）
河南省科技攻关项目(212102310629,212102310877) （212102310629,212102310877）
