Minjie Tian1, Xingjian Lin2, Liang Wu3, Jie Lu2, Yingdong Zhang4, Jingping Shi5. 1. Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, PR China; Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China. 2. Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China. 3. Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, PR China. 4. Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, PR China; Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China. Electronic address: zhangyingdong@aliyun.com. 5. Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China. Electronic address: profshijp@163.com.
Abstract
OBJECTIVE: The activation of renin angiotensin system is involved in multiple pathological processes. Growing evidence reveal that Angiotensin II (Ang II) contributes to the pathogenesis of Alzheimer disease (AD). However, the underlying mechanisms are still not fully understood. METHODS: In this study, the effect of Ang II on Aβ1-42 induced neurotoxicity was evaluated in PC12 cells. Apoptosis was examined by flow cytometry analysis and caspase-3 activity assay. Autophagy-related markers were also measured in each group. RESULTS: The results indicated that Ang II activated autophagy and triggered apoptosis in PC12 cells in a dose-dependent manner, as demonstrated byincreased LC3 II/I ratio and decreased p62 expression. Moreover, inhibition of autophagy by 3-methyladenine markedly attenuated the apoptosis caused by Ang II. In addition, an AT1R antagonist losartan, rather than the AT2R antagonist PD123319, completely reversed the Ang II induced autophagic activation and subsequent cell apoptosis. CONCLUSIONS: Taken together, our study strengthen the crucial function of Ang II/AT1R axis in the pathogenesis of AD in vitro. These findings have deepened our understanding on the role of Ang II in the pathogenesis of AD and support the use of AT1R antagonists for the treatment of this devastating neurodegenerative disease.
OBJECTIVE: The activation of renin angiotensin system is involved in multiple pathological processes. Growing evidence reveal that Angiotensin II (Ang II) contributes to the pathogenesis of Alzheimer disease (AD). However, the underlying mechanisms are still not fully understood. METHODS: In this study, the effect of Ang II on Aβ1-42 induced neurotoxicity was evaluated in PC12 cells. Apoptosis was examined by flow cytometry analysis and caspase-3 activity assay. Autophagy-related markers were also measured in each group. RESULTS: The results indicated that Ang II activated autophagy and triggered apoptosis in PC12 cells in a dose-dependent manner, as demonstrated byincreased LC3 II/I ratio and decreased p62 expression. Moreover, inhibition of autophagy by 3-methyladenine markedly attenuated the apoptosis caused by Ang II. In addition, an AT1R antagonist losartan, rather than the AT2R antagonist PD123319, completely reversed the Ang II induced autophagic activation and subsequent cell apoptosis. CONCLUSIONS: Taken together, our study strengthen the crucial function of Ang II/AT1R axis in the pathogenesis of AD in vitro. These findings have deepened our understanding on the role of Ang II in the pathogenesis of AD and support the use of AT1R antagonists for the treatment of this devastating neurodegenerative disease.
Authors: Caglar Cosarderelioglu; Lolita S Nidadavolu; Claudene J George; Ruth Marx-Rattner; Laura Powell; Qian-Li Xue; Jing Tian; Joy Salib; Esther S Oh; Luigi Ferrucci; Pervin Dincer; David A Bennett; Jeremy D Walston; Peter M Abadir Journal: J Gerontol A Biol Sci Med Sci Date: 2022-04-01 Impact factor: 6.591