title: The reduced autophagic response by oxidative stress in angiotensin II-induced hypertrophic H9C2 cells causes more apoptotic cell death.
abstract: Autophagy is an important process in the pathogenesis of cardiovascular diseases, and angiotensin II (Ang II) plays a causative role in the induction of cardiomyocyte autophagy. The purpose of this study was to explore whether, under conditions of oxidative stress, levels and types of cell death were different in untreated and Ang II-treated cardiomyocytes (H9C2 cells). Treatment with 20 µM Ang II induced cardiac hypertrophy in H9C2 cells, with increased expression of the hypertrophic markers c-Fos, ß-myosin heavy chain, atrial natriuretic factor (ANF), and brain natriuretic factor (BNF). Under normal conditions, there was no difference in the levels of autophagic vacuoles and apoptotic bodies in untreated and Ang II-treated H9C2 cells. However, oxidative stress generated by 100 µM H₂O₂ triggered autophagy in untreated control cells, but had a reduced effect in Ang II-induced hypertrophic cells, resulting in more cell death, and this was associated with a decrease in connexin 43 expression. Blocking this autophagic response with 3-methyladenine resulted in a significant increase in cell death and apoptosis of H9C2 cells but did not significantly affect the response of Ang II-treated cells. The autophagic response to 100 µM H₂O₂ provides a survival advantage for cells and this is reduced by Ang II treatment.
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei 10672, Taiwan.
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei 10672, Taiwan ronichen@ntu.edu.tw.
authors.forename: Hsiu-Ching
authors.initials: HC
authors.lastname: Hsu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei 10672, Taiwan.
authors.forename: Ming-Fong
authors.initials: MF
authors.lastname: Chen
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology*; D018384:Oxidative Stress; D051381:Rats
chemical_list: D000804:Angiotensin II; D006861:Hydrogen Peroxide
keywords: Angiotensin; apoptosis; autophagy; hypertrophy; oxidative stress