Role of Endothelin in the Circulatory Changes Associated with Small Bowel Strangulation Obstruction in Pigs: Effects of the Endothelin Receptor Antagonist Bosentan

2001 ◽  
Vol 96 (2) ◽  
pp. 224-232 ◽  
Author(s):  
J. Fevang ◽  
K. Øvrebø ◽  
O. Myking ◽  
K. Grong ◽  
K. Svanes
Keyword(s):  
Small Bowel ◽  
Receptor Antagonist ◽  
Endothelin Receptor Antagonist ◽  
Endothelin Receptor ◽  
Small Bowel Strangulation ◽  
Bowel Strangulation

Bosentan, an endothelin receptor antagonist, ameliorates collagen-induced arthritis: the role of TNF-α in the induction of endothelin system genes

2012 ◽  
Vol 61 (4) ◽  
pp. 337-348 ◽  
Author(s):  
Paula B. Donate ◽  
Thiago M. Cunha ◽  
Waldiceu A. Verri ◽  
Cristina M. Junta ◽  
Flavia O. Lima ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Endothelin Receptor Antagonist ◽  
Endothelin Receptor ◽  
Collagen Induced Arthritis ◽  
Endothelin System ◽  
Tnf Α

scholarly journals Inhibition of CPU0213, a Dual Endothelin Receptor Antagonist, on Apoptosis via Nox4-Dependent ROS in HK-2 Cells

2016 ◽  
Vol 39 (1) ◽  
pp. 183-192 ◽  
Author(s):  
Qing Li ◽  
Ji Li ◽  
Hua Shao ◽  
Xiao-Xue Li ◽  
Feng Yu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Protein Expression ◽  
Receptor Antagonist ◽  
High Glucose ◽  
Molecular Mechanisms ◽  
Annexin V ◽  
Endothelin Receptor Antagonist ◽  
Endothelin Receptor ◽  
O2 Production

Background/Aims: Our previous studies have indicated that a novel endothelin receptor antagonist CPU0213 effectively normalized renal function in diabetic nephropathy. However, the molecular mechanisms mediating the nephroprotective role of CPU0213 remain unknown. Methods and Results: In the present study, we first detected the role of CPU0213 on apoptosis in human renal tubular epithelial cell (HK-2). It was shown that high glucose significantly increased the protein expression of Bax and decreased Bcl-2 protein in HK-2 cells, which was reversed by CPU0213. The percentage of HK-2 cells that showed Annexin V-FITC binding was markedly suppressed by CPU0213, which confirmed the inhibitory role of CPU0213 on apoptosis. Given the regulation of endothelin (ET) system to oxidative stress, we determined the role of redox signaling in the regulation of CPU0213 on apoptosis. It was demonstrated that the production of superoxide (O2-.) was substantially attenuated by CPU0213 treatment in HK-2 cells. We further found that CPU0213 dramatically inhibited expression of Nox4 protein, which gene silencing mimicked the role of CPU0213 on the apoptosis under high glucose stimulation. We finally examined the role of CPU0213 on ET-1 receptors and found that high glucose-induced protein expression of endothelin A and B receptors was dramatically inhibited by CPU0213. Conclusion: Taken together, these results suggest that this Nox4-dependenet O2- production is critical for the apoptosis of HK-2 cells in high glucose. Endothelin receptor antagonist CPU0213 has an anti-apoptosis role through Nox4-dependent O2-.production, which address the nephroprotective role of CPU0213 in diabetic nephropathy.

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