Effect of rosiglitazone on NO and eNOS via PI3K/PKB signal pathways in cultured human umbilical vein endothelial cells.
- Author:
Jing WU
1
;
Min-xiang LEI
;
Xiao-yun XIE
;
Xiang-ling FENG
Author Information
1. Department of Endocrinology, Xiangya Hospital, Central South University, Changsha 410008, China. wujing0731@hotmail.com
- Publication Type:Journal Article
- MeSH:
Cells, Cultured;
Human Umbilical Vein Endothelial Cells;
drug effects;
metabolism;
Humans;
Nitric Oxide;
metabolism;
Nitric Oxide Synthase Type III;
metabolism;
Phosphatidylinositol 3-Kinases;
metabolism;
Phosphorylation;
drug effects;
Proto-Oncogene Proteins c-akt;
metabolism;
Rosiglitazone;
Signal Transduction;
drug effects;
Thiazolidinediones;
pharmacology
- From:
Journal of Central South University(Medical Sciences)
2007;32(5):824-830
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To observe the effect of rosiglitazone on the production of nitric oxide (NO) and the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) /the endothelial nitric oxide synthase (eNOS) in cultured human umbilical vein endothelial cells(HUVECs), and to investigate the mechanism of signal transduction of rosiglitazone in improving the endothelial function.
METHODS:HUVECs were treated with various concentrations of rosiglitazone. The NO level was measured using Griess Reaction in cell culture supernatants; the expressions of PI3K-, PKB- and eNOS mRNA were measured using RT-PCR; and the expressions of PKB, eNOS, and phosphorylation of PKB-Ser473, eNOS-Ser1177 were measured using Western Blot.
RESULTS:Rosiglitazone increased the endothelial NO production in a dose- and time-dependent manner in cultured HUVECs, and also increased the expression of PI3K mRNA and the phosphorylation of PKB-Ser473 and eNOS-Ser1177 in a concentration-dependent manner, with no alteration in the expression of PKB and eNOS in cultured HUVECs. N(w)-nitro-L- arginine methyl ester (L-NAME, eNOS synthase inhibitor) blocked the rosiglitazone-induced NO formation; LY294002 (a PI3K inhibitor) prevented the NO production; and the phosphorylation of eNOS and PKB was induced by rosiglitazone.
CONCLUSION:Treatment with rosiglitazone can increase the NO production and improve the endothelial function through up-regulating the PI3K/PKB/eNOS signal pathways in cultured HUVECs.
