赣南医学院学报2024，Vol.44Issue(5)：470-477,8.DOI:10.3969/j.issn.1001-5779.2024.05.005
血管紧张素转化酶2:乳酸的一个潜在靶点
Angiotensin converting enzyme 2:a potential target for lactate
摘要
Abstract
Objective:To explore the effects of angiotensin converting enzyme 2(ACE2)protein function and its effect mechanisms under L-lactate and D-lactate conditions.Methods:Protein structure prediction of ACE2 was performed by AlphaFold2,and molecular docking simulation analyses of ACE2 with L-lacyaye,D-lacate,pyruvate,and MLN-4760,which is a specific inhibitor of ACE2,were performed as a control for the positive results of this study.Based on the re-sults of molecular docking simulation analyses,the effects of L-lactate and D-lactate on ACE2 enzyme activity were de-tected using the Angiotensin Converting Enzyme 2(ACE2)Activity Fluorescence Assay Kit.HEK-293 cells were rou-tinely cultured and transfected with both RBD-Flag and ACE2-HA plasmid vectors before being treated with lactate and MLN-4760,respectively,and the level of binding of RBD to ACE2 was detected by co-IP.Results:Docking results showed that L-lactate and D-lactate may bind to the chloride binding site of ACE2,and further in vitro enzyme activity assays indicated that both L-lactate and D-lactate were able to inhibit ACE2 enzyme activity in a concentration-dependent manner,with the inhibitory effect of L-lactate being stronger than that of D-lactate on ACE2,and pyruvate has no signifi-cant effect on ACE2 activity.ACE2 is a key receptor mediating SARS-CoV-2 invasion into cells.The results of the co-IP experiments showed that L-lactate enhanced the binding of the SARS-CoV-2 viral S-protein RBD to ACE2,whereas the ACE2 inhibitor(MLN-4760)did not have a significant effect on the binding of RBD to ACE2.Conclusion:L-Lactate inhibits ACE2 enzyme activity and promotes binding of RBD to ACE2.关键词
乳酸/血管紧张素转换酶2/肾素-血管紧张素-醛固酮系统/糖尿病/高血压Key words
Lactate/Angiotensin converting enzyme 2(ACE2)/Renin-angiotensin-aldosterone system(RAAS)/Diabetes/Hypertension分类
医药卫生引用本文复制引用
苏晶,张源媛,黄犇犇,钟朕,刘先发,钟佳宁..血管紧张素转化酶2:乳酸的一个潜在靶点[J].赣南医学院学报,2024,44(5):470-477,8.基金项目
江西省自然科学基金重点项目(20224ACB206003) （20224ACB206003）
江西省自然科学基金面上项目(20232BAB206045) （20232BAB206045）
赣州市创新领军人才科学计划项目(2022CXRC8898) （2022CXRC8898）
江西省大学生创新创业训练计划项目(202210413007) （202210413007）
