Glutathione disrupts galectin-10 Charcot-Leyden crystal formation to possibly ameliorate eosinophil-based diseases such as asthma  

作　　者：Heya Na Hend Sayed Gabriela Jaramillo Ayala Xing Wang Yuhan Liu Jinyi Yu Tianhao Liu Kevin H.Mayo Jiyong Su 

机构地区：[1]Engineering Research Center of Glycoconjugates Ministry of Education,Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs,School of Life Sciences,Northeast Normal University,Changchun 130024,China [2]Department of Biochemistry,Molecular Biology&Biophysics,6-155 Jackson Hall,University of Minnesota,321 Church Street,Minneapolis,Minnesota 55455,USA

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第4期613-622,共10页生物化学与生物物理学报（英文版）

基　　金：the grants from the National Natural Science Foundation of China(No.32171255);Industrialization Cultivation Planning Project of Jilin Provincial Department of Education(No.JJKH20221168CY).

摘　　要：Charcot-Leyden crystals(CLCs)are the hallmark of many eosinophilic-based diseases,such as asthma.Here,we report that reduced glutathione(GSH)disrupts CLCs and inhibits crystallization of human galectin-10(Gal-10).GSH has no effect on CLCs from monkeys(Macaca fascicularis or M.mulatta),even though monkey Gal-10s contain Cys29 and Cys32.Interestingly,human Gal-10 contains another cysteine residue(Cys57).Because GSH cannot disrupt CLCs formed by the human Gal-10 variant C57A or inhibit its crystallization,the effects of GSH on human Gal-10 or CLCs most likely occur by chemical modification of Cys57.We further report the crystal structures of Gal-10 from M.fascicularis and M.mulatta,along with their ability to bind to lactose and inhibit erythrocyte agglutination.Structural comparison with human Gal-10 shows that Cys57 and Gln75 within the ligand binding site are responsible for the loss of lactose binding.Pull-down experiments and mass spectrometry show that human Gal-10 interacts with tubulinα-1B,with GSH,GTP and Mg^(2+)stabilizing this interaction and colchicine inhibiting it.Overall,this study enhances our understanding of Gal-10 function and CLC formation and suggests that GSH may be used as a pharmaceutical agent to ameliorate CLC-induced diseases.

关 键 词：ASTHMA Charcot-Leyden crystal GLUTATHIONE galectin-10 tubulinα-1B 

分 类 号：R562.25[医药卫生—呼吸系统]