典型文献
Inducement of ER Stress by PAD Inhibitor BB-Cl-Amidine to Effectively Kill AML Cells
文献摘要：
Objective:Acute myeloid leukemia(AML)is a highly heterogeneous and recurrent hematological malignancy.Despite the emergence of novel chemotherapy drugs,AML patients'complete remission(CR)remains unsatisfactory.Consequently,it is imperative to discover new therapeutic targets or medications to treat AML.Such epigenetic changes like DNA methylation and histone modification play vital roles in AML.Peptidylarginine deminase(PAD)is a protein family of histone demethylases,among which the PAD2 and PAD4 expression have been demonstrated to be elevated in AML patients,thus suggesting a potential role of PADs in the development or maintenance of AML and the potential for the identification of novel therapeutic targets.Methods:AML cells were treated in vitro with the pan-PAD inhibitor BB-Cl-Amidine(BB-Cl-A).The AML cell lines were effectively induced into apoptosis by BB-Cl-A.However,the PAD4-specific inhibitor GSK484 did not.Results:PAD2 played a significant role in AML.Furthermore,we found that BB-Cl-A could activate the endoplasmic reticulum(ER)stress response,as evidenced by an increase in phosphorylated PERK(p-PERK)and eIF2a(p-eIF2a).As a result of the ER stress activation,the BB-Cl-A effectively induced apoptosis in the AML cells.Conclusion:Our findings indicated that PAD2 plays a role in ER homeostasis maintenance and apoptosis prevention.Therefore,targeting PAD2 with BB-Cl-A could represent a novel therapeutic strategy for treating AML.
文献关键词：
中图分类号：
作者姓名：
Yan-ni SUN;Yan-ni MA;Xiao-qing JIA;Qi YAO;Jie-ping CHEN;Hui LI
作者机构：
Department of Hematology,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing 400038,China
文献出处：
引用格式：
[1]Yan-ni SUN;Yan-ni MA;Xiao-qing JIA;Qi YAO;Jie-ping CHEN;Hui LI-.Inducement of ER Stress by PAD Inhibitor BB-Cl-Amidine to Effectively Kill AML Cells)[J].当代医学科学(英文),2022(05):958-965
A类：
Inducement,Amidine,Peptidylarginine,deminase,PAD2,PADs,GSK484
B类：
Stress,by,Inhibitor,BB,Cl,Effectively,Kill,AML,Cells,Objective,Acute,myeloid,leukemia,highly,heterogeneous,recurrent,hematological,malignancy,Despite,emergence,novel,chemotherapy,drugs,patients,complete,remission,CR,remains,unsatisfactory,Consequently,imperative,discover,new,therapeutic,targets,medications,Such,epigenetic,changes,like,methylation,histone,modification,vital,roles,protein,family,demethylases,among,which,PAD4,expression,have,been,demonstrated,elevated,thus,suggesting,potential,development,maintenance,identification,Methods,cells,were,treated,vitro,pan,inhibitor,lines,effectively,induced,into,apoptosis,However,specific,did,not,Results,played,significant,Furthermore,found,that,could,activate,endoplasmic,reticulum,stress,response,evidenced,increase,phosphorylated,PERK,eIF2a,result,activation,Conclusion,Our,findings,indicated,plays,homeostasis,prevention,Therefore,targeting,represent,strategy,treating
AB值：
0.515116
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