title: Jak2/Stat1 pathway mediated tetrahydrobiopterin up-regulation contributes to nitric oxide overproduction in high-glucose cultured rat mesangial cells.
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.
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.
authors.forename: Jian-Yun
authors.initials: JY
authors.lastname: Wang
authors.forename: Shuai
authors.initials: S
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Qin
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Yin
mesh_terms: D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000633:toxicity; D002478:Cells, Cultured; D005947:Glucose / Q000633:toxicity*; D053614:Janus Kinase 2 / Q000096:biosynthesis*; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D050794:STAT1 Transcription Factor / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D050794:STAT1 Transcription Factor; C494081:Stat1 protein, rat; D001708:Biopterins; D009569:Nitric Oxide; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; C003402:sapropterin; D005947:Glucose
keywords: diabetic nephropathy; nitric oxide synthase; néphropathie diabétique; oxidative stress; stress oxydant; synthase d’oxyde nitrique