Chao Liang1, Fang Du1, Jing Cang2, Zhanggang Xue1. 1. Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China. 2. Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China. cangjing1998@126.com.
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.
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.
Authors: Ruben K Dagda; Irene Pien; Ruth Wang; Jianhui Zhu; Kent Z Q Wang; Jason Callio; Tania Das Banerjee; Raul Y Dagda; Charleen T Chu Journal: J Neurochem Date: 2013-11-13 Impact factor: 5.372
Authors: Matthew L Pearn; Yue Hu; Ingrid R Niesman; Hemal H Patel; John C Drummond; David M Roth; Katerina Akassoglou; Piyush M Patel; Brian P Head Journal: Anesthesiology Date: 2012-02 Impact factor: 7.892