Autophagy is a renoprotective mechanism during in vitro hypoxia and in vivo ischemia-reperfusion injury

Am J Pathol. 2010 Mar;176(3):1181-92. doi: 10.2353/ajpath.2010.090594. Epub 2010 Jan 14.


Autophagy mediates bulk degradation and recycling of cytoplasmic constituents to maintain cellular homeostasis. In response to stress, autophagy is induced and may either contribute to cell death or serve as a cell survival mechanism. Very little is known about autophagy in renal pathophysiology. This study examined autophagy and its pathological role in renal cell injury using in vitro and in vivo models of ischemia-reperfusion. We found that hypoxia (1% O2) induced autophagy in cultured renal proximal tubular cells. Blockade of autophagy by 3-methyladenine or small-interfering RNA knockdown of Beclin-1 and ATG5 (two key autophagic genes) sensitized the tubular cells to hypoxia-induced apoptosis. In an in vitro model of ischemia-reperfusion, autophagy was not induced by anoxic (0% O2) incubation in glucose-free buffer, but was induced during subsequent recovery/reperfusion period. In this model, suppression of autophagy also enhanced apoptosis. In vivo, autophagy was induced in kidney tissues during renal ischemia-reperfusion in mice. Autophagy was not obvious during the ischemia period, but was significantly enhanced during reperfusion. Inhibition of autophagy by chloroquine and 3-methyladenine worsened renal ischemia/reperfusion injury, as indicated by renal function, histology, and tubular apoptosis. Together, the results demonstrated autophagy induction during hypoxic and ischemic renal injury. Under these pathological conditions, autophagy may provide a protective mechanism for cell survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy* / drug effects
  • Autophagy-Related Protein 5
  • Beclin-1
  • Cell Line
  • Chloroquine / pharmacology
  • Cytoprotection* / drug effects
  • Gene Knockdown Techniques
  • Hypoxia / complications*
  • Hypoxia / pathology*
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / ultrastructure
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / pathology
  • Kidney Tubules, Proximal / ultrastructure
  • Mice
  • Mice, Inbred C57BL
  • Proteins / metabolism
  • Rats
  • Reperfusion Injury / complications*
  • Reperfusion Injury / pathology*
  • Vacuoles / drug effects
  • Vacuoles / pathology
  • Vacuoles / ultrastructure


  • Apoptosis Regulatory Proteins
  • Atg5 protein, rat
  • Autophagy-Related Protein 5
  • Beclin-1
  • Becn1 protein, rat
  • Proteins
  • 3-methyladenine
  • Chloroquine
  • Adenine