Cathepsin L induced PC-12 cell apoptosis via activation of B-Myb and regulation of cell cycle proteins  

作　　者：Xiao Shen Yi-fan Zhao Shu-qing Xu Long Wang Hui-min Cao Ying Cao Ying Zhu Yan Wang Zhong-qin Liang 

机构地区：[1]department of Pharmacology,College of Pharmaceutical Sciences,Soochow University,215123 Suzhou,China [2]Department of Pharmacy,The First People's Hospital of Wujiang,215000 Suzhou,China

出　　处：《Acta Pharmacologica Sinica》2019年第11期1394-1403,共10页中国药理学报（英文版）

基　　金：the National Natural Science Foundation of China(Grant nos.81773768 and 81671252);the Priority Academic Program Development of the Jiangsu Higher Education Institutes(PAPD).

摘　　要：Cathepsin L(CTSL),a cysteine protease,is responsible for the degradation of a variety of proteins.It is known to participate in neuronal apoptosis associated with abnormal cell cycle.However,the mechanisms underlying CTSL-induced cell apoptosis remain largely unclear.We reported here that rotenone caused an activation of CTSL expression in PC-12 cells,while knockdown of CTSL by small interfering RNAs or its inhibitor reduced the rotenone-induced cell cycle arrest and apoptosis.Moreover,elevation of CTSL and increased-apoptosis were accompanied by induction of B-Myb,a crucial cell cycle regulator.We found that B-Myb was increased in rotenone-treated PC-12 cells and knockdown of B-Myb ameliorated rotenone-stimulated cell apoptosis.Further analysis demonstrated that CTSL influenced the expression of B-Myb as suppression of CTSL activity led to a decreased B-Myb expression,whereas overexpression of CTSL resulted in B-Myb induction.Reduction of B-Myb in CTSL-overexpressing cells revealed that regulation of cell cycle-related proteins,including cyclin A and cyclin B1,through CTSL was mediated by the transcription factor B-Myb.In addition,we demonstrated that the B-Myb target,Bim,and its regulator,Egr-1,which was also associated with CTSL closely,were both involved in rotenone-induced apoptosis in PC-12 cells.Our data not only revealed the role of CTSL in rotenoneinduced neuronal apoptosis,but also indicated the involvement of B-Myb in CTSL-related cell cycle regulation.

关 键 词：CATHEPSIN L B-MYB CYCLIN B1 CYCLIN A cell cycle apoptosis 

分 类 号：R73[医药卫生—肿瘤]