title: 2-Bromopalmitate impairs neural stem/progenitor cell proliferation, promotes cell apoptosis and induces malformation in zebrafish embryonic brain.
abstract: 2-Bromopalmitate (2BP) is a widely used palmitoylation inhibitor. Besides, it has been reported that 2BP can inhibit T-cell activation, making it a potential immunosuppressor for the treatment of autoimmune diseases. Although the important roles of palmitoylation in a neural system have been noted during the past decades, the effect of 2BP on neural development is still not very clear. In this study, we demonstrated that 25 μM-100 μM 2BP exposure caused apparent neural malformation in the presumptive brains of zebrafish embryos at 14 hpf. Further studies implied that the mRNA quantities and distributions of neural stem/progenitor cell (NSPC) markers (neurog1, sox2, and sox3) in the affected regions of 50 μM 2BP treated embryos significantly decreased. In addition, we found that 2BP impaired the NSPC proliferation at 10 hpf and 14 hpf as well as promoted cell apoptosis at 14 hpf, consistent with which the interference with FGF/ERK signaling pathway was also detected. For the first time, this study provided information about the toxicity and teratogenicity of 2BP for neural development in vivo.
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China; Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, PR China.
authors.forename: Xueran
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Du
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China.
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China; Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China.
authors.forename: Tong
authors.initials: T
authors.lastname: Shao
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China. Electronic address: aijunhao@sdu.edu.cn.
authors.forename: Aijun
authors.initials: A
authors.lastname: Hao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D004625:Embryo, Nonmammalian / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D058953:Neural Stem Cells / Q000187:drug effects*; D010168:Palmitates / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
chemical_list: D010168:Palmitates; C022776:2-bromopalmitate
keywords: 2-Bromopalmitate; FGF signaling pathway; Neural development; Neural stem/progenitor cells; Palmitoylation; Zebrafish