Autoantibody against Cardiac β_1-Adrenoceptor Induces Apoptosis in Cultured Neonatal Rat Cardiomyocytes  

作　　者：Yan GAO Hui-Rong LIU Rong-Rui ZHAO Jian-Ming ZHI 

机构地区：[1]Department of Cardiovascular Physiology, Shanxi Medical University, Taiyuan 030001, China [2]Department of Physiology, Shanghai Jiaotong University, College of Basic Medicine, Shanghai 200025, China

出　　处：《Acta Biochimica et Biophysica Sinica》2006年第7期443-449,共7页生物化学与生物物理学报（英文版）

摘　　要：To clarify whether apoptosis is involved in the injury processes induced by autoantibody against cardiac β1-adrenoceptor, we investigated the biological and apoptotic effects of antibodies on cultured neonatal rat cardiomyocytes. Wistar rats were immunized with peptides corresponding to the second extracellular loop of the β1-adrenoceptor to induce the production of anti-β1-adrenoceptor antibodies in the sera. Immunoglobulin （Ig） G in the sera was detected using synthetic antigen enzyme-linked immunosorbent assay and purified using the diethylaminoethyl cellulose ion exchange technique. Apoptosis of cardiomyocytes was evaluated using agarose gel electrophoresis and flow cytometry. Our results showed that the positive serum IgG greatly increased the beating rates of cardiomyocytes and showed an ＂agonist-like＂ activity. Furthermore, positive serum IgG induced cardiomyocyte apoptosis after treatment with β1- adrenoceptor overstimulation for 48 h. The effects of monoclonal antibody against β1-adrenoceptor were also found to be similar to those of positive serum IgG. It was suggested that the autoantibody could induce cardiomyocyte apoptosis by excessive stimulation of β1-adrenoceptor.To clarify whether apoptosis is involved in the injury processes induced by autoantibody against cardiac β1-adrenoceptor, we investigated the biological and apoptotic effects of antibodies on cultured neonatal rat cardiomyocytes. Wistar rats were immunized with peptides corresponding to the second extracellular loop of the β1-adrenoceptor to induce the production of anti-β1-adrenoceptor antibodies in the sera. Immunoglobulin （Ig） G in the sera was detected using synthetic antigen enzyme-linked immunosorbent assay and purified using the diethylaminoethyl cellulose ion exchange technique. Apoptosis of cardiomyocytes was evaluated using agarose gel electrophoresis and flow cytometry. Our results showed that the positive serum IgG greatly increased the beating rates of cardiomyocytes and showed an ＂agonist-like＂ activity. Furthermore, positive serum IgG induced cardiomyocyte apoptosis after treatment with β1- adrenoceptor overstimulation for 48 h. The effects of monoclonal antibody against β1-adrenoceptor were also found to be similar to those of positive serum IgG. It was suggested that the autoantibody could induce cardiomyocyte apoptosis by excessive stimulation of β1-adrenoceptor.

关 键 词：Β1-ADRENOCEPTOR rat cardiomyocyte AUTOANTIBODY APOPTOSIS 

分 类 号：R542.2[医药卫生—心血管疾病]