Schisantherin A protects renal tubular epithelial cells from hypoxia/reoxygenation injury through the activation of PI3K/Akt signaling pathway

2018 ◽  
Vol 32 (7) ◽  
pp. e22160 ◽  
Author(s):  
Jiachuan Gong ◽  
Xuezhen Wang
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Tubular Epithelial Cells ◽  
Akt Signaling Pathway ◽  
Renal Tubular Epithelial Cells ◽  
Reoxygenation Injury ◽  
Renal Tubular ◽  
Schisantherin A ◽  
Hypoxia Reoxygenation

Ceramide synthase is essential for endonuclease-mediated death of renal tubular epithelial cells induced by hypoxia-reoxygenation

2005 ◽  
Vol 288 (2) ◽  
pp. F308-F314 ◽  
Author(s):  
Alexei G. Basnakian ◽  
Norishi Ueda ◽  
Xiaoman Hong ◽  
Valentin E. Galitovsky ◽  
Xiaoyan Yin ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Ceramide Synthase ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Ceramide Level ◽  
Reoxygenation Injury ◽  
Renal Tubular ◽  
Ceramide Generation ◽  
Hypoxia Reoxygenation

Ceramide is known to play a role in the cell signaling pathway involved in apoptosis. Most studies suggest that enhanced ceramide generation is the result of hydrolysis of sphingomyelin by sphingomyelinases. However, the role of ceramide synthase in enhanced ceramide generation has not been previously examined in hypoxia-reoxygenation injury. In the present study, we demonstrated that 60-min hypoxia of rat renal tubular epithelial NRK-52E cells in a gas chamber with 95% N2-5% CO2 with glucose deprivation resulted in a significant increase in ceramide generation. The ceramide level further increased after reoxygenation for 60 min. Exposure of cells to hypoxia-reoxygenation resulted in a significant increase in ceramide synthase activity without any significant change in acid or neutral sphingomyelinase. The hypoxia-reoxygenation of NRK-52E cells was also associated with the release of endonuclease G (EndoG) from mitochondria to cytoplasm measured by Western blot analysis and endonuclease activity assay. It further led to the fragmentation of DNA and cell death. A specific inhibitor of ceramide synthase, fumonisin B1 (50 μM), suppressed hypoxia-reoxygenation-induced ceramide generation and provided protection against hypoxia-reoxygenation-induced EndoG release, DNA fragmentation, and cell death. Taken together, our data suggest that hypoxia-reoxygenation results in an activation of ceramide synthase rather than sphingomyelinase and that ceramide synthase-dependent ceramide generation is a key modulator of EndoG-mediated cytotoxicity in hypoxia-reoxygenation injury to renal tubular epithelial cells.

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