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- Title
Jak2/Stat1 pathway mediated tetrahydrobiopterin up-regulation contributes to nitric oxide overproduction in high-glucose cultured rat mesangial cells.
- Authors
Wang, Jian-Yun; Liu, Shuai; Qin, Na; Yang, Qian-Qian; Guo, Hao; Zhang, Fan; Yin, Xiao-Xing
- Abstract
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.
- Subjects
STAT proteins; TETRAHYDROBIOPTERIN; PHYSIOLOGICAL effects of nitric oxide; CELL culture; DIABETIC nephropathies; DISEASE progression; LABORATORY rats
- Publication
Canadian Journal of Physiology & Pharmacology, 2015, Vol 93, Issue 1, p81
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2014-0255