Abstract
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 (H2O2)-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 H2O2 for different times (1, 3, and 6 h). Then HUVECs were pretreated with different concentrations of propofol (10, 25, and 50 μM), followed by H2O2 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 H2O2 treatment (0.5 mM, 3 h). After treatment, oxidative stress, p38 MAPK phosphorylation, transcription factor NF-κB activation, nitric oxide synthase (NOS) expression, nitric oxide (NO) production, and monocyte adhesion were measured. We observed H2O2 treatment significantly induced oxidative stress, which could be attenuated by 25 μM propofol pretreatment. In addition, H2O2 treatment significantly induced p38 MAPK phosphorylation, NF-κB activation, NOS expression, and NO production. More importantly, our study showed these H2O2-induced changes were attenuated by propofol or SB203580 pretreatment. Further, we measured monocyte adhesion as a marker of endothelial cell dysfunction. H2O2 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-κB activity, decreasing NOS expression, reducing NO production, could protect HUVECs which are exposed to oxidative stress and becoming dysfunctional.
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This project was supported by the National Nature Foundation of China (Grant# 30772078).
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Chen, J., Gu, Y., Shao, Z. et al. Propofol protects against hydrogen peroxide-induced oxidative stress and cell dysfunction in human umbilical vein endothelial cells. Mol Cell Biochem 339, 43–54 (2010). https://doi.org/10.1007/s11010-009-0368-y
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DOI: https://doi.org/10.1007/s11010-009-0368-y