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Autophagy and apoptosis in tubular cells following unilateral ureteral obstruction are associated with mitochondrial oxidative stress.

Authors: Xu, Y  Ruan, S  Wu, X  Chen, H  Zheng, K  Fu, B 
Citation: Xu Y, etal., Int J Mol Med. 2013 Mar;31(3):628-36. doi: 10.3892/ijmm.2013.1232. Epub 2013 Jan 8.
Pubmed: (View Article at PubMed) PMID:23314838
DOI: Full-text: DOI:10.3892/ijmm.2013.1232

Tubular epithelial loss has been shown to be responsible for the formation of atubular glomeruli leading to nephron decomposition and interstitial fibrosis in obstructive uropathy. Cells undergoing apoptosis and autophagic cell death play an important role in this process, yet the mechanisms are not fully understood. In this study, we aimed to investigate whether autophagy cooperating with apoptosis is associated with mitochondrial damage and whether oxidative stress plays an important role in the loss of tubular epithelium following unilateral ureteral obstruction. In this model, we demonstrated that there is coexistence of autophagy and apoptosis with tubular atrophy in obstructed proximal tubules. After unilateral ureteral obstruction (UUO), autophagy in proximal tubular cells was enhanced steadily up to 7 days in the obstructed kidney and declined thereafter, while apoptosis was induced in a time-dependent manner from 3 to 14 days. Mitochondrial structure and number also changed during UUO. Lipid peroxidation products, NOX4, and NADPH oxidase activity were also increased in the obstructed renal cortex, and peaked at 7 days. In vitro, we showed that H2O2 induced mitochondrial injury leading to autophagy and apoptosis through the Beclin 1 pathway and interference with Bcl-2 expression. Thus, our data demonstrate that oxidative stress leading to mitochondrial damage and driven autophagy-dependent cell death and apoptosis are important mechanisms of tubular decomposition in obstructive nephropathy.

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CRRD Object Information
CRRD ID: 11561927
Created: 2016-11-11
Species: All species
Last Modified: 2016-11-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.