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

Mi Bai, Ruochen Che, Yue Zhang, Yanggang Yuan, Chunhua Zhu, Guixia Ding, Zhanjun Jia, Songming Huang, Aihua Zhang
2016 AJP - Renal Physiology  
oxygen species-initiated autophagy opposes aldosterone-induced podocyte injury. 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
more » ... 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 Ϫ7 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 H 2O2 (10 Ϫ4 mol/l) application remarkably elevated podocyte autophagy. After treatment with N-acetylcysteine, the autophagy induced by Aldo or H 2O2 was markedly attenuated, suggesting a key role of ROS in mediating autophagy formation in podocytes. Inhibition of ROS could also lessen Aldoinduced podocyte injury. Taken together, our findings suggest that ROS-triggered autophagy played a protective role against Aldoinduced podocyte injury, and targeting autophagy in podocytes may represent a new therapeutic strategy for the treatment of podocytopathy. podocyte; aldosterone; autophagy; apoptosis; reactive oxygen species PODOCYTES not only participate in forming the mechanical and electric charge barrier of the glomerular filtration membrane but also play key roles in maintaining the normal opening of the glomerular capillary loop, alleviating the impact of hydrostatic pressure, producing the glomerular basement membrane matrix, and maintaining the homeostasis of glomerular basement membrane metabolism (13). Podocytes, as an important component of the filtration barrier, are terminally differentiated cells and do not proliferate (23). Consequently, loss of podocytes can cause mesangial expansion, proteinuria, deterioration of glomerulosclerosis, and, ultimately, the progressive loss of kidney function (15). RESULTS Aldo induced podocyte damage. Aldo (10 Ϫ7 mol/l) induced podocyte apoptosis in a time-dependent manner. After 24 h of Aldo treatment, the apoptosis rate was significantly increased (P Ͻ 0.05) compared with the control group. After 48 h of stimulation, the apoptosis rate was further increased by 41.8% F670
doi:10.1152/ajprenal.00409.2015 pmid:26764202 fatcat:bjypvr7xenecdlurcwhckxjiva