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Pink1 attenuates propofol-induced apoptosis and oxidative stress in developing neurons

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Abstract

Background

The underlying mechanisms of propofol-induced neurotoxicity in developing neurons are still not completely understood. We examined the role of PTEN-induced kinase 1 (Pink1), an antioxidant protein, in propofol-induced apoptosis in developing neurons.

Materials and methods

Primary hippocampal neurons isolated from neonatal Sprague–Dawley rats were exposed to propofol 20 μM for 2, 4, 6 and 12 h. Subsequently, neurons underwent overexpression and knockdown of Pink1, followed by propofol exposure (20 μM, 6 h). Neuron apoptosis was detected by terminal transferase deoxyuridine triphosphate-biotin nick-end labeling (TUNEL). Reactive oxygen species (ROS) production in neurons was detected by using a 2,7-dichlorodihydro-fluorescein diacetate probe and target protein or mRNA levels were analyzed by Western blotting or real-time polymerase chain reaction.

Results

Propofol treatment time-dependently increased the number of TUNEL-positive neurons and the expression levels of cleaved caspase-3 and B-cell lymphoma 2 (BcL-2) associated X protein, but decreased expression levels of BcL-2. Furthermore, propofol treatment time-dependently reduced the expression levels of Pink1 mRNA and protein. ROS production and the markers of oxidative stress, 2,4-dinitrophenol and 4-hydroxynonenal, were increased by propofol treatment. However, these propofol-induced changes were significantly restored by Pink1 overexpression.

Conclusions

Pink1 plays an important role in neuronal apoptosis induced by propofol. Our results may provide some new insights in propofol-induced neurotoxicity in developing neurons.

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Authors and Affiliations

  1. Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China

    Chao Liang, Fang Du, Jing Cang & Zhanggang Xue

Authors
  1. Chao Liang
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  2. Fang Du
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  3. Jing Cang
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  4. Zhanggang Xue
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Corresponding author

Correspondence to Jing Cang.

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Conflict of interest

The authors declare that they have no competing interests.

Funding

This work was supported by the Natural Science Foundation of China (Grant no. 81400930).

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Cite this article

Liang, C., Du, F., Cang, J. et al. Pink1 attenuates propofol-induced apoptosis and oxidative stress in developing neurons. J Anesth 32, 62–69 (2018). https://doi.org/10.1007/s00540-017-2431-2

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  • DOI: https://doi.org/10.1007/s00540-017-2431-2

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