title: Reactive oxygen species-initiated autophagy opposes aldosterone-induced podocyte injury.
abstract: Evidence has demonstrated that aldosterone (Aldo) is involved in the development and progression of chronic kidney diseases. The purpose of the present study was to investigate the role of autophagy in Aldo-induced podocyte damage and the underlying mechanism. Mouse podocytes were treated with Aldo in the presence or absence of 3-methyladenine andN-acetylcysteine. Cell apoptosis was investigated by detecting annexin V conjugates, apoptotic bodies, caspase-3 activity, and alterations of the podocyte protein nephrin. Autophagy was evaluated by measuring the expressions of light chain 3, p62, beclin-1, and autophagy-related gene 5. Aldo (10-7mol/l) induced podocyte apoptosis, autophagy, and downregulation of nephrin protein in a time-dependent manner. Aldo-induced apoptosis was further promoted by the inhibition of autophagy via 3-methyladenine and autophagy-related gene 5 small interfering RNA pretreatment. Moreover, Aldo time dependently increased ROS generation, and H2O2(10-4mol/l) application remarkably elevated podocyte autophagy. After treatment withN-acetylcysteine, the autophagy induced by Aldo or H2O2was markedly attenuated, suggesting a key role of ROS in mediating autophagy formation in podocytes. Inhibition of ROS could also lessen Aldo-induced podocyte injury. Taken together, our findings suggest that ROS-triggered autophagy played a protective role against Aldo-induced podocyte injury, and targeting autophagy in podocytes may represent a new therapeutic strategy for the treatment of podocytopathy.
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.|Institute of Pediatrics, Nanjing Medical University, Nanjing, China; and.
authors.forename: Mi
authors.initials: M
authors.lastname: Bai
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.|Institute of Pediatrics, Nanjing Medical University, Nanjing, China; and.
authors.forename: Ruochen
authors.initials: R
authors.lastname: Che
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.|Institute of Pediatrics, Nanjing Medical University, Nanjing, China; and.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yanggang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.|Institute of Pediatrics, Nanjing Medical University, Nanjing, China; and.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.|Institute of Pediatrics, Nanjing Medical University, Nanjing, China; and.
authors.forename: Guixia
authors.initials: G
authors.lastname: Ding
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.|Institute of Pediatrics, Nanjing Medical University, Nanjing, China; and.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.|Institute of Pediatrics, Nanjing Medical University, Nanjing, China; and.
authors.forename: Songming
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China; zhaihua@njmu.edu.cn.|Institute of Pediatrics, Nanjing Medical University, Nanjing, China; and.
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D000071187:Autophagy-Related Protein 5 / Q000378:metabolism; D000071186:Beclin-1 / Q000378:metabolism; D015536:Down-Regulation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; C113267:nephrin; D000450:Aldosterone; C025946:3-methyladenine; D006861:Hydrogen Peroxide; D000225:Adenine; D000111:Acetylcysteine
keywords: aldosterone; apoptosis; autophagy; podocyte; reactive oxygen species