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

  • Authors:
    • Yanfang Xu
    • Shiwei Ruan
    • Xiaonan Wu
    • Hong Chen
    • Ke Zheng
    • Binbin Fu
  • View Affiliations

  • Published online on: January 8, 2013     https://doi.org/10.3892/ijmm.2013.1232
  • Pages: 628-636
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Abstract

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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March 2013
Volume 31 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
APA
Xu, Y., Ruan, S., Wu, X., Chen, H., Zheng, K., & Fu, B. (2013). Autophagy and apoptosis in tubular cells following unilateral ureteral obstruction are associated with mitochondrial oxidative stress. International Journal of Molecular Medicine, 31, 628-636. https://doi.org/10.3892/ijmm.2013.1232
MLA
Xu, Y., Ruan, S., Wu, X., Chen, H., Zheng, K., Fu, B."Autophagy and apoptosis in tubular cells following unilateral ureteral obstruction are associated with mitochondrial oxidative stress". International Journal of Molecular Medicine 31.3 (2013): 628-636.
Chicago
Xu, Y., Ruan, S., Wu, X., Chen, H., Zheng, K., Fu, B."Autophagy and apoptosis in tubular cells following unilateral ureteral obstruction are associated with mitochondrial oxidative stress". International Journal of Molecular Medicine 31, no. 3 (2013): 628-636. https://doi.org/10.3892/ijmm.2013.1232