Angiotensin II triggers autophagy and apoptosis in PC12 cell line: An in vitro Alzheimer’s disease model
| Autor: | Xingjian Lin, Jie Lu, Minjie Tian, Jingping Shi, Ying-Dong Zhang, Liang Wu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pyridines PC12 cell line Apoptosis Pharmacology Models Biological PC12 Cells Losartan Receptor Angiotensin Type 1 Pathogenesis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Alzheimer Disease Renin–angiotensin system Autophagy medicine Animals Molecular Biology Chemistry Angiotensin II General Neuroscience Imidazoles Neurotoxicity Neurodegenerative Diseases medicine.disease Rats 030104 developmental biology Neurology (clinical) Angiotensin II Type 1 Receptor Blockers 030217 neurology & neurosurgery Developmental Biology medicine.drug |
| Zdroj: | Brain Research. 1718:46-52 |
| ISSN: | 0006-8993 |
| Popis: | 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 by increased 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. |
| Databáze: | OpenAIRE |
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