Relationship between Mecp2 and NFκb signaling during neural differentiation of P19 cells

• Published in: Brain research Vol. 1490; no. 15; pp. 35 - 42
• Main Authors: O'Driscoll, Cliona, Kaufmann, Walter E, Bressler, Joseph
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15-01-2013; Elsevier
• Subjects: Biological and medical sciences; Blotting, Western; brain; carcinoma; Cell Differentiation - genetics; Cell Differentiation - physiology; Cell differentiation, maturation, development, hematopoiesis; Cell Line, Tumor; Cell physiology; Development; Enzyme Activators - pharmacology; Fundamental and applied biological sciences. Psychology; Genes, Reporter; Humans; Immunohistochemistry; Methyl DNA binding protein 2; Methyl-CpG-Binding Protein 2 - genetics; Methyl-CpG-Binding Protein 2 - physiology; Molecular and cellular biology; Neurology; neurons; Neurons - physiology; NF-kappa B - antagonists & inhibitors; NF-kappa B - genetics; NF-kappa B - physiology; NFκB; P19 embryonic carcinoma cells; Pluripotent Stem Cells; protein kinase C; Protein Kinase C - metabolism; Real-Time Polymerase Chain Reaction; reporter genes; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; signal transduction; Signal Transduction - genetics; Signal Transduction - physiology; Tetradecanoylphorbol Acetate - pharmacology; Tretinoin - pharmacology; tubulin; Tumor necrosis factor; Tumor Necrosis Factor-alpha - pharmacology; tumor necrosis factors; Development; Methyl DNA binding protein 2; NFκB; Tumor necrosis factor; P19 embryonic carcinoma cells; Embryo; Cytokine; Binding protein; Signal transduction; Neuron; DNA; Transcription factor NFκB; Differentiation
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2012.10.041

Abstract The pluripotent P19 embryo carcinoma cell line was studied to determine a signaling pathway regulating MeCP2 expression. P19 cells were induced to differentiate into neurons by RA and express β -III tubulin at one day after induction and synaptophysin by 7 days. MeCP2 was first observed after β -III tubulin expression was detected and continued to rise over the course of differentiation. Both Mecp 2 e1 and e 2 mRNA forms progressively increased in differentiating cells. MeCP2 expression was increased by tumor necrosis factor (TNF) in early differentiating cells, which was blocked by NFκB inhibitors. TNF did not increase MeCP2 expression in naïve cells. Moreover, TNF did not increase NFκB reporter gene activity in naïve cells even though increases were observed in early differentiating cells. The protein kinase C activator phorbol 12-myristate 13-acetate (PMA) increased MeCP2 expression in naïve P19 cells, which was also blocked by NFκB inhibitors. Interestingly, PMA increased NFκB reporter gene activity in naïve cells. Finally, PMA, but not TNF, induced IκBα degradation in naïve P19 cells. Taken together, our data indicates that MeCP2 expression is regulated in part by signaling pathways involving NFκB.