Abstract
Propofol (2,6-diisopropylphenol) is a widely used general anesthetic with anti-oxidant activities. This study aims to investigate protective capacity of propofol against hydrogen peroxide (H2O2)-induced oxidative injury in neural cells and whether the anti-oxidative effects of propofol occur through a mechanism involving the modulation of NADPH oxidase (NOX) in a manner of calcium-dependent. The rat differentiated PC12 cell was subjected to H2O2 exposure for 24 h to mimic a neuronal in vitro model of oxidative injury. Our data demonstrated that pretreatment of PC12 cells with propofol significantly reversed the H2O2-induced decrease in cell viability, prevented H2O2-induced morphological changes, and reduced the ratio of apoptotic cells. We further found that propofol attenuated the accumulation of malondialdehyde (biomarker of oxidative stress), counteracted the overexpression of NOX core subunit gp91phox (NOX2) as well as the NOX activity following H2O2 exposure in PC12 cells. In addition, blocking of L-type Ca2+ channels with nimodipine reduced H2O2-induced overexpression of NOX2 and caspase-3 activation in PC12 cells. Moreover, NOX inhibitor apocynin alone or plus propofol neither induces a significant downregulation of NOX activity nor increases cell viability compared with propofol alone in the PC12 cells exposed to H2O2. These results demonstrate that the protective effects of propofol against oxidative injury in PC12 cells are mediated, at least in part, through inhibition of Ca2+-dependent NADPH oxidase.
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Abbreviations
- NADPH:
-
Nicotinamide adenine dinucleotide phosphate
- NOX:
-
NADPH oxidase
- ROS:
-
Reactive oxygen species
- H2O2 :
-
Hydrogen peroxide
- PC12 cell:
-
Rat pheochromocytoma cell
- MDA:
-
Malondialdehyde
- CNS:
-
Central nervous system
- AD:
-
Alzheimer’s disease
- PD:
-
Parkinson’s disease
- TBI:
-
Traumatic brain injury
- [Ca2+]i :
-
Cytosolic Ca2+
- ·OH:
-
Hydroxyl radical
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- ANOVA:
-
One-way analysis of variance
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Acknowledgments
This work was supported by Guangzhou International Science and Technology Cooperation Project (No. 2012J5100019) and Braun Research Fund for Anesthesiology (No. BBDF-2014-016). Our work was also supported by Grants from the National Nature Science Foundation of China (31471030), the Research foundation of Department of Science and Technology of Guangzhou (201510010208), and Department of Teaching of Sun Yat-sen University.
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Chen, Xh., Zhou, X., Yang, Xy. et al. Propofol Protects Against H2O2-Induced Oxidative Injury in Differentiated PC12 Cells via Inhibition of Ca2+-Dependent NADPH Oxidase. Cell Mol Neurobiol 36, 541–551 (2016). https://doi.org/10.1007/s10571-015-0235-1
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DOI: https://doi.org/10.1007/s10571-015-0235-1