Angiotensin Ⅱ type Ⅰ receptor agonistic autoantibody-induced apoptosis in neonatal rat cardiomyocytes is dependent on the generation of tumor necrosis factor-α  

作　　者：Weiran Chai Wenhui Zhang Zhu Jin Yiping Feng Yanping Kuang Jianming Zhi 

机构地区：[1]Department of Assisted Reproductive Technology,Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China [2]Department of Physiology,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [3]Department of Clinical Laboratory,Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China

出　　处：《Acta Biochimica et Biophysica Sinica》2012年第12期984-990,共7页生物化学与生物物理学报（英文版）

基　　金：supported by a grant from the National Natural Science Foundation of China(31101070).

摘　　要：Angiotensin II type I receptor agonistic autoantibodies （AT1-AA） are related to pre-eclampsia and hypertension and have a direct effect of stimulating the production of tumor necrosis factor-alpha （TNF-α in the placenta. TNF-α is a known mediator of apoptosis. However, few studies have reported the role of TNF-α and its relation- ship within AT1-AA-induced apoptosis of cardiomyocytes. In this study, neonatal rat cardiomyocytes were treated with various concentrations of AT1-AA. The apoptosis of neonatal rat cardiomyocytes was determined using TUNEL assay and flow cytometry. The level of secreted TNF-oL was measured by enzyme-linked immunosorbent assay, and caspase-3 activity was measured by a fluoro- genic protease assay kit. AT1 receptor blockade and TNF inhibitor were added to determine whether they could inhibit the apoptotic effect of AT1-AA. Results showed that AT1-AA induced the apoptosis of neonatal rat cardio- myocytes in a dose-dependent and time-dependent manner. AT1-AA increased TNF secretion and caspase-3 activities. AT1 receptor blockade completely abrogated AT1-AA-induced TNF-α secretion, caspase-3 activation, and cardiomyocyte apoptosis. TNF-α receptor inhibitor significantly attenuated AT1-AA-induced neonatal rat car- diomyocyte apoptosis. AT1-AA in the plasma of preeclamptic patients promoted neonatal rat cardiomyocyte apoptosis through a TNF-caspase signaling pathway.Angiotensin II type I receptor agonistic autoantibodies （AT1-AA） are related to pre-eclampsia and hypertension and have a direct effect of stimulating the production of tumor necrosis factor-alpha （TNF-α in the placenta. TNF-α is a known mediator of apoptosis. However, few studies have reported the role of TNF-α and its relation- ship within AT1-AA-induced apoptosis of cardiomyocytes. In this study, neonatal rat cardiomyocytes were treated with various concentrations of AT1-AA. The apoptosis of neonatal rat cardiomyocytes was determined using TUNEL assay and flow cytometry. The level of secreted TNF-oL was measured by enzyme-linked immunosorbent assay, and caspase-3 activity was measured by a fluoro- genic protease assay kit. AT1 receptor blockade and TNF inhibitor were added to determine whether they could inhibit the apoptotic effect of AT1-AA. Results showed that AT1-AA induced the apoptosis of neonatal rat cardio- myocytes in a dose-dependent and time-dependent manner. AT1-AA increased TNF secretion and caspase-3 activities. AT1 receptor blockade completely abrogated AT1-AA-induced TNF-α secretion, caspase-3 activation, and cardiomyocyte apoptosis. TNF-α receptor inhibitor significantly attenuated AT1-AA-induced neonatal rat car- diomyocyte apoptosis. AT1-AA in the plasma of preeclamptic patients promoted neonatal rat cardiomyocyte apoptosis through a TNF-caspase signaling pathway.

关 键 词：angiotensin Ⅱ type Ⅰ receptor agonistic autoantibodies(AT1-AA) apoptosis tumor necrosis factor-alpha neonatal rat cardiomyocytes 

分 类 号：Q786[生物学—分子生物学] Q343.1