| Autor: |
Wei Jing Liu, Bi-Hua Xu, Lin Ye, Dong Liang, Hong-Luan Wu, Yuan-Yuan Zheng, Jian Kun Deng, Benyi Li, Hua-feng Liu |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Renal Physiology; 3/15/2015, Vol. 308 Issue 6, pF639-F649, 11p |
| Abstrakt: |
Lysosomal membrane permeabilization (LMP) has been shown to cause the release of cathepslns and other hydrolases from the lysosomal lumen to the cytosol and initiate a cell death pathway. Whether proteinuria triggers LMP in renal tubular epithelial cells (TECs) to accelerate the progression of renal tubulointerstitial injury remains unclear. In the present study, we evaluated TEC injury as well as changes in lysosomal number, volume, activity, and membrane integrity after urinary protein overload in vivo and in vitro. Our results revealed that neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 levels were significantly increased in the urine of patients with minimal change nephrotic syndrome (MCNS) and the culture supernatant of HK-2 cells treated by urinary proteins extracted from MCNS patients. Urinary protein overload also induced apoptotlc cell death in HK-2 cells. Importantly, we found that lysosomal volume and number were markedly increased in TECs of patients with MCNS and HK-2 cells overloaded with urinary proteins. However, lysosome function, as assessed by proteolytic degradation of DQ-ovalbumin and cathepsln- B and cathepsln-L activities, was decreased in HK-2 cells overloaded with urinary proteins. Furthermore, urinary protein overload led to a diffuse cytoplasmic immunostaining pattern of cathepsln-B and irregular immunostaining of lysosome-assoclated membrane protein- 1, accompanying a reduction in intracellular acidic components, which could be improved by pretreatment with antioxidant. Taken together, our results indicate that overloading of urinary proteins caused LMP and lysosomal dysfunction at least partly via oxidative stress in TECs. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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