Endoplasmic reticulum stress contributed to β1-adrenoceptor autoantibody-induced reduction of autophagy in cardiomyocytes  

作　　者：Li Wang Na Ning Changtu Wang Xiaohong Hou Yuan Yuan Yanan Ren Cong Sun Zi Yan Xiaohui Wang Huirong Liu 

机构地区：[1]Department of Pathology,School of Basic Medical Sciences,Shanxi Medical University,Taiyuan 030001,China [2]Laboratory of Morphology,School of Basic Medical Sciences,Shanxi Medical University,Taiyuan 030001,China [3]Department of Physiology,School of Basic Medical Sciences,Shanxi Medical University,Taiyuan 030001,China [4]Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China

出　　处：《Acta Biochimica et Biophysica Sinica》2019年第10期1016-1025,共10页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.31871177 and 31401006);Scientific and Technological Innovation Program of Higher Education Institutions in Shanxi Province(No.201802059);the Graduate Educational Innovation Project of Shanxi Province(No.2018129).

摘　　要：Autophagy reduction has been confirm ed as an im portant mechanism in apoptosis induction.Our previous study showed that decreased autophagy induced by Pi-adrenoceptor autoantibodies(Pi-AAs)enhanced cardiom yocyte apoptosis and contributed to heart failure progression.Endoplasmic reticulum stress(ERS)is known to be an im portant mechanism in intracellular homeostasis and is closely related to autophagy.However,ERS in pi-AA-induced autophagy dysfunction of cardiom yocytes remains unclear.In this study,we used an active im m unization rat model and H9c2 cardiom yocytes to study the role of ERS in Pi-AA-induced autophagy.Results showed that prolonged action of Pi-AAs significantly reduced the autophagy of myocardial tissues and H9c2 cardiom yocytes,and ERS and its related apoptotic pathways were significantly activated.Moreover,mRFP-GFP-LC3 double-labeled adenoviruses were used to detect cardiom yocyte autophagic flux to confirm that Pi-AAs caused a significant decrease in autophagic flux in H9c2 cardiom yocytes.The ERS inhibitor,4-phenylbutyrate(4-PBA),partially attenuated the β1-AA-induced reduction of cardiom yocyte autophagy,consistent w ith the effect of the m am m alian target of rapam ycin inh ibito r rapamycin(Rapa).Compared to the pretreatm ent with 4-PBA or Rapa alone,pretreatm ent w ith the com bination of 4-PBA and Rapa had a greater effect on attenuating the pi-AA-induced decrease in autophagy and Pi-AA-induced apoptosis in cardiomyocytes.This study provides an experim ental basis fo r the role of Pi-AAs in the homeostatic maintenance of cardiom yocytes in patients w ith heart failure w ith respect to autophagy and ERS.

关 键 词：ADRENERGIC RECEPTOR AUTOANTIBODY endoplasmic reticulum stress AUTOPHAGY apoptosis 

分 类 号：R73[医药卫生—肿瘤]