• Chao Liang, Fang Du, Jing Cang, and Zhanggang Xue.
• Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.
• J Anesth. 2018 Feb 1; 32 (1): 62-69.

BackgroundThe 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 MethodsPrimary 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.ResultsPropofol 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.ConclusionsPink1 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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