title: Propofol inhibits high glucose-induced PP2A expression in human umbilical vein endothelial cells.
abstract: Perioperative hyperglycemia is a common clinical metabolic disorder. Hyperglycemia could induce endothelial apoptosis, dysfunction and inflammation, resulting in endothelial injury. Propofol is a widely used anesthetic drug in clinical settings. Our previous studies indicated that propofol, via inhibiting high glucose-induced phosphatase A2 (PP2A) expression, attenuated high glucose-induced reactive oxygen species (ROS) accumulation, thus improving endothelial apoptosis, dysfunction and inflammation. However, the mechanisms by which propofol attenuated high glucose-induced PP2A expression is still obscure. In the present study, we examined how propofol attenuates high glucose-induced endothelial PP2A expression. Compared with 5mM glucose treatment, 15mM glucose up-regulated expression and activity of PP2A, increased cAMP response element binding protein (CREB), Ca2+-calmodulin dependent kinase II (CaMK II) phosphorylation and Ca2+accumulation. More importantly, propofol decreased PP2A expression and activity, attenuated CREB, CaMK II phosphorylation and Ca2+accumulation in a concentration-dependent manner. Moreover, we demonstrated that the effect of propofol was similar to that of MK801, an inhibitor of NMDA receptor. In contrast, rapastinel, an activator of NMDA receptor, antagonized the effect of propofol. Also, the effect of KN93, an inhibitor of CaMK II, was similar to that of propofol, except KN93 had no effect on 15mM glucose-mediated Ca2+accumulation. Our data indicated that propofol, via inhibiting NMDA receptor, attenuated 15mM glucose-induced Ca2+accumulation, CaMK II and CREB phosphorylation, thus inhibiting PP2A expression and improving 15mM glucose-induced endothelial dysfunction and inflammation.
authors.affiliation: Department of Anesthesiology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Qichao
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Anaesthesiology, Xinjiang Medical University, Affiliated Tumour Hospital, Xinjiang, PR China.
authors.forename: Wenming
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Xiangyuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China. Electronic address: zhu_mm@126.com.
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhu
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D015742:Propofol / Q000494:pharmacology*; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
chemical_list: D018686:Anesthetics, Intravenous; D000893:Anti-Inflammatory Agents; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D016194:Receptors, N-Methyl-D-Aspartate; D013481:Superoxides; D009569:Nitric Oxide; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054648:Protein Phosphatase 2; D005947:Glucose; D002118:Calcium; D015742:Propofol
keywords: CREB; CaMK II; High glucose; PP2A