Cisplatin-induced macroautophagy occurs prior to apoptosis in proximal tubules in vivo

Clin Exp Nephrol. 2010 Apr;14(2):112-22. doi: 10.1007/s10157-009-0254-7. Epub 2009 Dec 15.


Background: Autophagy is an intracellular bulk degradation process induced by cell starvation. Autophagy was recently reported to be induced by various stresses such as hypoxia, ischemia/reperfusion, toxins, and denatured proteins, and to affect cell survival and death. Light chain 3-II (LC3-II) is specifically located on double membrane-bound autophagosomes that envelop disused proteins or organelles.

Method: Transgenic mice in which green fluorescent protein (GFP) was fused to LC3 (LC3-GFP) were administered cisplatin (20 mg/kg). After euthanasia at times between 0 and 72 h, kidneys were excised for immunohistochemical analyses. Microscopic examinations of the generated NRK-52E cell lines stably transfected with LC3-GFP, and Western blot analyses of NRK-52E cells, were undertaken after cisplatin treatment with or without autophagy inhibitors and beclin 1 small interfering RNA (siRNA).

Results: Autophagosomes increased in the proximal tubular cells of transgenic mice from 12 h after cisplatin injection (20 mg/kg). The time course for this was faster than those for tubular necrosis and apoptosis. Autophagosomes also increased in NRK-52E cells after cisplatin treatment, with the time course for this being faster than that for apoptosis. When autophagy was suppressed by autophagy inhibitors or beclin 1 siRNA, the level of apoptosis was also suppressed.

Conclusion: Autophagy occurs in proximal tubular cells after cisplatin treatment and is involved in cell death in renal tubular injury. Our data suggest that autophagy is a kind of cell damage index and that cells with activated autophagy will be scavenged by apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / physiopathology
  • Animals
  • Apoptosis / physiology
  • Autophagy / drug effects
  • Autophagy / physiology*
  • Cisplatin / pharmacology*
  • Kidney Tubules, Proximal / metabolism*
  • Male
  • Mice
  • Mice, Transgenic


  • Cisplatin