Propofol protects human umbilical vein endothelial cells from cisplatin-induced injury.

The anticancer drug cisplatin can up-regulate endothelial adhesion molecule expression, and trigger vascular endothelial injury. Propofol, an intravenous anesthetic, can inhibit endothelial adhesion molecule expression in some situations. Here, we explored whether and how propofol improved cisplatin-induced up-regulation of endothelial adhesion molecules in human umbilical vein endothelial cells. Compared with control group, cisplatin reduced endothelial nitric oxide synthase dimer/monomer ratio, activated protein kinase C and enhanced endothelial nitric oxide synthase-Thr495 phosphorylation, decreased nitric oxide production, augmented intercellular adhesion molecule 1 expression and monocyte-endothelial adhesion. These cisplatin-mediated effects were attenuated by propofol treatment. Nω-Nitro-L-arginine methyl ester hydrochloride, a nitric oxide synthase inhibitor, inhibited the effect of propofol on cisplatin-induced intercellular adhesion molecule 1 expression. Propofol improved cisplatin-mediated tetrahydrobiopterin reduction and nitrotyrosine overexpression. Compared with control group, cisplatin and PMA, a protein kinase C activator, both increased endothelial nitric oxide synthase-Thr495 phosphorylation, while propofol and GFX, a protein kinase C inhibitor, both decreased cisplatin-induced endothelial nitric oxide synthase-Thr495 phosphorylation. Our data indicated that propofol, via reducing cisplatin-induced endothelial nitric oxide synthase uncoupling and endothelial nitric oxide synthase-Thr495 phosphorylation, restored nitric oxide production, intercellular adhesion molecule 1 expression and monocyte-endothelial interaction.

Zhu M ，Chen J ，Yin H ，Jiang H ，Wen M ，Miao C ... -  《-》

Propofol protects against high glucose-induced endothelial dysfunction in human umbilical vein endothelial cells.

Zhu M ，Chen J ，Tan Z ，Wang J ... -  《-》

Propofol ameliorates endothelial inflammation induced by hypoxia/reoxygenation in human umbilical vein endothelial cells: Role of phosphatase A2.

Hypoxia/reoxygenation (H/R) induces endothelial inflammation with augmentation of endothelial adhesion molecules over-expression. Propofol was reported to attenuate endothelial adhesion molecule expression in some situations. Here, we examined the molecular mechanism for how propofol restored H/R-mediated up-regulation of endothelial adhesion molecules in human umbilical vein endothelial cells (HUVECs). Compared with the control group, H/R up-regulated expression of Pin-1 and PP2A, increased p66(Shc)-Ser(36) phosphorylation, induced p66(Shc) mitochondrial translocation, O2(-) accumulation and NF-κB activation, and decreased eNOS-Ser(1177) phosphorylation and nitric oxide (NO) production, thus up-regulating expression of endothelial adhesion molecules and increasing mononuclear-endothelial interaction. More importantly, except that propofol had no effect on H/R-induced p66(Shc)-Ser(36) phosphorylation, most of H/R-mediated changes were alleviated by propofol, resulting in the reduction of endothelial adhesion molecules expression and mononuclear-endothelial adhesion. Moreover, we demonstrated the protective effect of propofol on H/R-induced endothelial inflammation was similar to that of calyculin A, an inhibitor of PP2A. In contrast, FTY720, an activator of PP2A, antagonized the effect of propofol. Our data indicated that propofol down-regulated PP2A expression, leading to reduced dephosphorylation of p66(Shc)-Ser(36) and eNOS-Ser(1177), which is associated with ROS accumulation and NO reduction, resulting in inhibition of endothelial adhesion molecule expression and mononuclear-endothelial interaction.

Zhu M ，Ding J ，Jiang H ，Kong L ，Sun Z ，Chen J ，Miao C ... -  《-》

Propofol protects against high glucose-induced endothelial apoptosis and dysfunction in human umbilical vein endothelial cells.

Zhu M ，Wen M ，Sun X ，Chen W ，Chen J ，Miao C ... -  《-》

Arginase Inhibition Restores Peroxynitrite-Induced Endothelial Dysfunction via L-Arginine-Dependent Endothelial Nitric Oxide Synthase Phosphorylation.

Nguyen MC ，Park JT ，Jeon YG ，Jeon BH ，Hoe KL ，Kim YM ，Lim HK ，Ryoo S ... -  《-》