Propofol protects against hydrogen peroxide-induced oxidative stress and cell dysfunction in human umbilical vein endothelial cells.
Propofol has been reported to protect vascular endothelial cells against oxidative stress and dysfunction, but the underlying mechanisms are not clear. In this study, we studied hydrogen peroxide (H(2)O(2))-induced oxidative stress and cell dysfunction in human umbilical vein endothelial cells (HUVECs) and especially, their modulation by propofol. HUVECs were treated with different concentrations (0.1 and 0.5 mM) of H(2)O(2) for different times (1, 3, and 6 h). Then HUVECs were pretreated with different concentrations of propofol (10, 25, and 50 microM), followed by H(2)O(2) treatment (0.5 mM, 3 h). In another set of experiments, we pretreated cells with p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, followed by H(2)O(2) treatment (0.5 mM, 3 h). After treatment, oxidative stress, p38 MAPK phosphorylation, transcription factor NF-kappaB activation, nitric oxide synthase (NOS) expression, nitric oxide (NO) production, and monocyte adhesion were measured. We observed H(2)O(2) treatment significantly induced oxidative stress, which could be attenuated by 25 microM propofol pretreatment. In addition, H(2)O(2) treatment significantly induced p38 MAPK phosphorylation, NF-kappaB activation, NOS expression, and NO production. More importantly, our study showed these H(2)O(2)-induced changes were attenuated by propofol or SB203580 pretreatment. Further, we measured monocyte adhesion as a marker of endothelial cell dysfunction. H(2)O(2) increased the adhesion of monocytes to HUVECs, and propofol pretreatment reduced the adhesion in a fashion similar to SB203580. We concluded that propofol, by inhibiting p38 MAPK and NF-kappaB activity, decreasing NOS expression, reducing NO production, could protect HUVECs which are exposed to oxidative stress and becoming dysfunctional.
Chen
Jiawei
J
Department of Anesthesiology, Shanghai Cancer Center, Fudan University, No. 270 DongAn Road, Shanghai 200032, People's Republic of China.
Gu
Yuechao
Y
Shao
Zhiming
Z
Luo
Jianmin
J
Tan
Zhiming
Z
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015227:Lipid Peroxidation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018686:Anesthetics, Intravenous; D016328:NF-kappa B; D016877:Oxidants; D012333:RNA, Messenger; D013481:Superoxides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D048051:p38 Mitogen-Activated Protein Kinases; D015742:Propofol