Xiaoqing Fan1, Haoran Yang2,3, Lizhu Hu2,3, Delong Wang1, Ruiting Wang1, Aijun Hao4, Xueran Chen5,6. 1. Department of Anesthesiology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China (USTC), No. 17, Lujiang Road, Hefei, 230001, Anhui, China. 2. Department of Laboratory Medicine, Hefei Cancer Hospital, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, 230031, Anhui, China. 3. Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, 230031, Anhui, China. 4. Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Mental Disorders, Department of Anatomy and Histoembryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, No. 44, Wenhua Xi Road, Jinan, 250012, Shandong, China. aijunhao@sdu.edu.cn. 5. Department of Laboratory Medicine, Hefei Cancer Hospital, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, 230031, Anhui, China. xueranchen@cmpt.ac.cn. 6. Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, 230031, Anhui, China. xueranchen@cmpt.ac.cn.
Abstract
BACKGROUND: Propofol can have adverse effects on developing neurons, leading to cognitive disorders, but the mechanism of such an effect remains elusive. Here, we aimed to investigate the effect of propofol on neuronal development in zebrafish and to identify the molecular mechanism(s) involved in this pathway. METHODS: The effect of propofol on neuronal development was demonstrated by a series of in vitro and in vivo experiments. mRNA injections, whole-mount in situ hybridization and immunohistochemistry, quantitative real-time polymerase chain reaction, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, 5-ethynyl-2'-deoxyuridine labeling, co-immunoprecipitation, and acyl-biotin exchange labeling were used to identify the potential mechanisms of propofol-mediated zisp expression and determine its effect on the specification of retinal cell types. RESULTS: Propofol impaired the specification of retinal cell types, thereby inhibiting neuronal and glial cell formation in retinas, mainly through the inhibition of Zisp expression. Furthermore, Zisp promoted the stabilization and secretion of a soluble form of the membrane-associated protein Noggin-1, a specific palmitoylation substrate. CONCLUSIONS: Propofol caused a severe phenotype during neuronal development in zebrafish. Our findings established a direct link between an anesthetic agent and protein palmitoylation in the regulation of neuronal development. This could be used to investigate the mechanisms via which the improper use of propofol might result in neuronal defects.
BACKGROUND:Propofol can have adverse effects on developing neurons, leading to cognitive disorders, but the mechanism of such an effect remains elusive. Here, we aimed to investigate the effect of propofol on neuronal development in zebrafish and to identify the molecular mechanism(s) involved in this pathway. METHODS: The effect of propofol on neuronal development was demonstrated by a series of in vitro and in vivo experiments. mRNA injections, whole-mount in situ hybridization and immunohistochemistry, quantitative real-time polymerase chain reaction, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, 5-ethynyl-2'-deoxyuridine labeling, co-immunoprecipitation, and acyl-biotin exchange labeling were used to identify the potential mechanisms of propofol-mediated zisp expression and determine its effect on the specification of retinal cell types. RESULTS:Propofol impaired the specification of retinal cell types, thereby inhibiting neuronal and glial cell formation in retinas, mainly through the inhibition of Zisp expression. Furthermore, Zisp promoted the stabilization and secretion of a soluble form of the membrane-associated protein Noggin-1, a specific palmitoylation substrate. CONCLUSIONS:Propofol caused a severe phenotype during neuronal development in zebrafish. Our findings established a direct link between an anesthetic agent and protein palmitoylation in the regulation of neuronal development. This could be used to investigate the mechanisms via which the improper use of propofol might result in neuronal defects.
Authors: Alaa El-Din El-Husseini; Eric Schnell; Srikanth Dakoji; Neal Sweeney; Qiang Zhou; Oliver Prange; Catherine Gauthier-Campbell; Andrea Aguilera-Moreno; Roger A Nicoll; David S Bredt Journal: Cell Date: 2002-03-22 Impact factor: 41.582
Authors: S Shanmugalingam; C Houart; A Picker; F Reifers; R Macdonald; A Barth; K Griffin; M Brand; S W Wilson Journal: Development Date: 2000-06 Impact factor: 6.868