Journal article
Autophagy Is a Renoprotective Mechanism During in Vitro Hypoxia and in Vivo Ischemia-Reperfusion Injury
The American journal of pathology, Vol.176(3), pp.1181-1192
03/2010
DOI: 10.2353/ajpath.2010.090594
PMCID: PMC2832141
PMID: 20075199
Abstract
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% O
2
) 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% O
2
) 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.
Details
- Title: Subtitle
- Autophagy Is a Renoprotective Mechanism During in Vitro Hypoxia and in Vivo Ischemia-Reperfusion Injury
- Creators
- Man Jiang - Charlie Norwood VA Medical CenterKebin Liu - Charlie Norwood VA Medical CenterJia Luo - University of KentuckyZheng Dong - Charlie Norwood VA Medical Center
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.176(3), pp.1181-1192
- Publisher
- American Society for Investigative Pathology
- DOI
- 10.2353/ajpath.2010.090594
- PMID
- 20075199
- PMCID
- PMC2832141
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Grant note
- DOI: 10.13039/100000048, name: American Cancer Society, award: RSG-09-209-01-TBG; DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs; DOI: 10.13039/100000002, name: National Institutes of Health, award: CA133085, DK58831, DK67738
- Language
- English
- Date published
- 03/2010
- Academic Unit
- Pathology
- Record Identifier
- 9984186552902771
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