title: Different effects of histone deacetylase inhibitors nicotinamide and trichostatin A (TSA) in C17.2 neural stem cells.
abstract: Histone deacetylase inhibitors are involved in proliferation, apoptosis, cell cycle, mRNA transcription, and protein expression in various cells. However, the molecular mechanism underlying such functions is still not fully clear. In this study, we used C17.2 neural stem cell (NSC) line as a model to evaluate the effects of nicotinamide and trichostatin A (TSA) on cell characteristics. Results show that nicotinamide and TSA greatly inhibit cell growth, lead to cell morphology changes, and effectively induce cell apoptosis in a dose-dependent manner. Western blot analyses confirmed that nicotinamide significantly decreases the expression of bcl-2 and p38. Further insight into the molecular mechanisms shows the suppression of phosphorylation in eukaryotic initiation factor 4E-binding protein 1 (4EBP1) by nicotinamide, whereas, an increased expression of bcl-2 and p38 and phosphorylation of 4EBP1 by TSA. However, both nicotinamide and TSA significantly increase the expression of cytochrome c (cyt c). These results strongly suggest that bcl-2, p38, cyt c, and p-4EBP1 could suppress proliferation and induce apoptosis of C17.2 NSCs mediated by histone deacetylase inhibitors, nicotinamide and TSA, involving different molecular mechanisms.
authors.affiliation: Laboratory of Molecular Neurobiology, School of Life Sciences, Institute of Systems Biology, Shanghai University, No. 99 Shangda Rd, Shanghai 200444, People's Republic of China. Wangbao4321567@163.com
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Cheng
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Tieqiao
authors.initials: T
authors.lastname: Wen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D039642:Eukaryotic Initiation Factors; D005786:Gene Expression Regulation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects; D051379:Mice; D058953:Neural Stem Cells / Q000187:drug effects*; D009536:Niacinamide / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039642:Eukaryotic Initiation Factors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D009536:Niacinamide; C012589:trichostatin A; D045304:Cytochromes c; D048051:p38 Mitogen-Activated Protein Kinases