Reactive oxygen species-initiated autophagy opposes aldosterone-induced podocyte injury

American Journal of Physiology. Renal Physiology
Mi BaiAihua Zhang

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 and N-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 (10-7 mol/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 (10-4 mol/l) application remarkably elevated podocyte autophagy. After treatment with N-acetylcysteine, the autophagy induced by Aldo or H2O2 was markedly attenuated, suggesting a key role of ROS in mediating autophagy formation in podocytes. Inhibition of RO...Continue Reading

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Citations

Jan 14, 2017·Renal Failure·Xu DengAihua Zhang
Jan 6, 2017·American Journal of Physiology. Renal Physiology·Mi BaiAihua Zhang
Aug 7, 2019·International Journal of Molecular Sciences·Gur P KaushalLuis A Juncos
Oct 10, 2020·Archives of Virology·Fatemeh Hosseini HeydarabadiFarzaneh Sheikholeslami
Nov 6, 2020·Journal of Cellular and Molecular Medicine·Jing-Wei GaoPin-Ming Liu

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