The effects of the GLP-1 analog liraglutide upon TNF-伪-induced injury of the human umbilical vein endothelial cells (HUVECs) were evaluated. First, ROS induced by TNF-伪 was measured by staining with CM-H2DCFDA. Intracellular ROS production of HUVECs was significantly decreased in a dose-dependent manner until 30 nM while liraglutide inhibited the induction of gp91phox and p22phox, subunit of NADPH oxidase, by TNF-伪鈰?In addition, protein levels of SOD-2, catalase and GPx were significantly increased by liraglutide. Second, rapid translocation of PKC-伪 into the membrane following TNF-伪 was evident. Liraglutide significantly inhibited this very rapid TNF-伪-induced translocation of PKC-伪 into membrane at 2.5 min. Third, liraglutide significantly inhibited NF-魏B activation and upregulated I-魏B family while phosphorylation of IKK-伪/尾, which is upstream of NF-魏B signaling, was also downregulated after 15 min of TNF-伪 treatment. Finally, liraglutide inhibited apoptosis of HUVEC and expression of Pentraxin-3 induced by TNF-伪.
Liraglutide exerts marked anti-oxidative and anti-inflammatory effects on endothelial cells with inhibition of PKC-伪, NADPH oxidase, NF-魏B signaling and upregulation of protective anti-oxidative enzymes.