PPAR-α Agonist Fenofibrate Upregulates Tetrahydrobiopterin Level through Increasing the Expression of Guanosine 5′-Triphosphate Cyclohydrolase-I in Human Umbilical Vein Endothelial Cells
Figure 4
Fenofibrate increases GTPCH-I protein levels in HUVECs, as demonstrated by Western blot analyses. (a) Cells were treated for 24 h with increasing concentrations of fenofibrate. (b) The level of GTPCH-I after fenofibrate treatment reached maximum at 12 hours and maintained a high level for a long time. (c) GW6471 antagonizes fenofibrate-induced increase in GTPCH-I protein level, WY14643 increases GTPCH-I protein level similarly to the effect of fenofibrate. Dates are means ± SD in three experiments. (a, b): * versus control group; (c) *, # versus control group. (d) Proposed scheme: Fenofibrate not only promotes the expression of eNOS, but also up-regulates the level of GTPCH-I, contributing to the increase of BH4, which could promote the activity of eNOS, thus resulting the increase of NO and decrease of ROS.
