Autophagy Protects Renal Tubular Cells Against Ischemia / Reperfusion Injury in a Time-Dependent Manner

• Published in: Cellular physiology and biochemistry Vol. 36; no. 1; pp. 285 - 298
• Main Authors: Guan, Xuejing, Qian, Yingying, Shen, Yue, Zhang, Lulu, Du, Yi, Dai, Huili, Qian, Jiaqi, Yan, Yucheng
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Cell Physiol Biochem Press GmbH & Co KG 01.01.2015
• Subjects: 3-methyladenine; Adenine - analogs & derivatives; Adenine - pharmacology; Animals; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Cell Survival - drug effects; Cells, Cultured; Gene Expression Regulation - drug effects; Hypoxia/reoxygenation; Ischemia/reperfusion; Kidney Tubules - drug effects; Kidney Tubules - metabolism; Kidney Tubules - pathology; Male; Mice; Original Paper; Rapamycin; Reperfusion Injury - metabolism; Reperfusion Injury - prevention & control; Sirolimus - pharmacology; Time Factors; Rapamycin; Ischemia/reperfusion; Autophagy; Hypoxia/reoxygenation; 3-methyladenine
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000374071

Background/Aims: Autophagy is a dynamic catabolic process that maintains cellular homeostasis. Whether it plays a role in promoting cell survival or cell death in the process of renal ischemia/reperfusion (I/R) remains controversial, partly because renal autophagy is usually examined at a certain time point. Therefore, monitoring of the whole time course of autophagy and apoptosis may help better understand the role of autophagy in renal I/R. Methods: Autophagy and apoptosis were detected after mice were subjected to bilateral renal ischemia followed by 0-h to 7-day reperfusion, exposure of TCMK-1 cells to 24-h hypoxia, and 2 to 24-h reoxygenation. The effect of autophagy on apoptosis was assessed in the presence of autophagy inhibitor 3-methyladenine (3-MA) and autophagy activator rapamycin. Results: Earlier than apoptosis, autophagy increased from 2-h reperfusion, reached the maximum at day 2, and then began declining from day 3 when renal damage had nearly recovered to normal. Exposure to 24-h hypoxia induced autophagy markedly, but it decreased drastically after 4 and 8-h reoxygenation, which was accompanied with increased cell apoptosis. Inhibition of autophagy with 3-MA increased the apoptosis of renal tubular cells during I/R in vivo and hypoxia/reoxygenation (H/R) in vitro. In contrast, activation of autophagy by rapamycin significantly alleviated renal tissue damage and tubular cell apoptosis in the two models. Conclusion: Autophagy was induced in a time-dependent manner and occurred earlier than the onset of cell apoptosis as an early response that played a renoprotective role during renal I/R and cell H/R. Up-regulation of autophagy may prove to be a potential strategy for the treatment of acute kidney injury.