Abstract
Oxidative stress contributes to myocardial ischemia-reperfusion injury, which causes cardiomyocyte death and precipitate life-threatening heart failure. Propofol has been proposed to protect cells or tissues against oxidative stress. However, the mechanisms underlying its beneficial effects are not fully elucidated. In the present study, we employed an in vitro oxidative injury model, in which rat cardiac H9c2 cells were treated with H2O2, and investigated roles of propofol against oxidative stress. Propofol treatment reduced H2O2-induced apoptotic cell death. While H2O2 induced expression of the antioxidant enzyme HO-1, propofol further increased HO-1 mRNA and protein levels. Propofol also promoted nuclear localization of Nrf2 in the presence of H2O2. Knockdown of Nrf2 using siRNA suppressed propofol-inducible Nrf2 and expression of Nrf2-downstream antioxidant enzyme. Knockdown of Nrf2 suppressed the propofol-induced cytoprotection. In addition, Nrf2 overexpression induced nuclear localization of Nrf2 and HO-1 expression. These results suggest that propofol exerts antioxidative effects by inducing nuclear localization of Nrf2 and expression of its downstream enzyme in cardiac cells. Finally, we examined the effect of propofol on cardiomyocytes using myocardial ischemia-reperfusion injury models. The expression level of Nrf2 protein was increased at 15 min after reperfusion in the ischemia-reperfusion and propofol group compared with ischemia-reperfusion group in penumbra region. These results suggest that propofol protects cells or tissues from oxidative stress via Nrf2/HO-1 cascade.
Highlights
H2O2 induced Heme oxygenase-1 (HO-1) protein (3.0-fold of control) and propofol further increased HO-1 protein level (3.9-fold of control). These results indicate that propofol increased HO-1 expression under oxidative stress
It is widely accepted that mitochondria play a key role in the development of oxidative stress, and the major endogenous sources of reactive oxygen species (ROS) are localized to mitochondria
We showed that propofol and H2O2 co-treatment increased the expression of HO-1 by promoting NF-E2-related factor 2 (Nrf2) nuclear localization in H9c2 cells
Summary
In addition to its anesthetic effects, propofol reportedly protects cells or tissues from oxidative stress [5, 6]. Tsuchiya et al [9] demonstrated that propofol could induce apoptosis in cultured human promyelocytic leukemia HL-60 cells via activation of the cell surface death receptor pathway and the mitochondrial pathway. These discrepancies may be attributed to differences in cell types and/or in experimental paradigms. Whether propofol has beneficial or harmful effects on particular cell types or tissues is clinically important, since propofol is commonly used in surgery, in which the human body receives invasive stress
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