Endothelin-1 Inhibits Induction of Nitric Oxide Synthase and GTP Cyclohydrolase I in Rat Mesangial Cells

Pharmacology ◽  
1996 ◽  
Vol 53 (4) ◽  
pp. 241-249 ◽  
Author(s):  
Junichi Hirahashi ◽  
Toshio Nakaki ◽  
Keiichi Hishikawa ◽  
Takeshi Marumo ◽  
Toshio Yasumori ◽  
...  
2015 ◽  
Vol 93 (1) ◽  
pp. 81-89 ◽  
Author(s):  
Jian-Yun Wang ◽  
Shuai Liu ◽  
Na Qin ◽  
Qian-Qian Yang ◽  
Hao Guo ◽  
...  

Nitric oxide (NO) is crucial for the progression of early diabetic nephropathy (DN). It is important to clarify the mechanism for the production of NO in mesangial cells (MCs). In this study, the amounts/activities of related factors such as reactive oxygen species (ROS), NO, 3 isoforms of nitric oxide synthase (NOS), tetrahydrobiopterin (BH4), GTP cyclohydrolase I (GTPCH I), Jak2, and Stat1 were determined using high-glucose cultured rat MCs. The results showed that the production of BH4 under oxidative stress was strongly stimulated by its rate-limiting enzyme GTP cyclohydrolase, which increased the expression and activity of inducible NOS to facilitate NO synthesis. Furthermore, the relative quantities of activated-Jak2 and activated-Stat1 were increased. Therefore, Jak2/Stat1 pathway mediated BH4 up-regulation can contribute to excessive NO in high-glucose cultured MCs. Our results will be helpful for screening new targets to improve the therapy for early DN.


1995 ◽  
Vol 48 (6) ◽  
pp. 1893-1899 ◽  
Author(s):  
Karl-Friedrich Beck ◽  
Markus G. Mohaupt ◽  
R. Bernd Sterzel ◽  
Stephanie with technical assistance from Peters ◽  
Hans Fees

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