Different effects of histone deacetylase inhibitors nicotinamide and trichostatin A (TSA) in C17.2 neural stem cells
Different effects of histone deacetylase inhibitors nicotinamide and trichostatin A (TSA) in C17.2 neural stem cells
复制标题
DOI：
10.1007/s00702-012-0786-y
复制
发表时间：
2012-03
影响因子：
3.3
通讯作者：
Haifeng Wang;Hua Cheng;Kai Wang;T. Wen
中科院分区：
文献类型：
--
作者：
Haifeng Wang;Hua Cheng;Kai Wang;T. Wen
组蛋白去乙酰化酶抑制剂参与各种细胞的增殖、凋亡、细胞周期、mRNA转录和蛋白质表达。然而，这些功能背后的分子机制仍然不完全清楚。本研究以C17.2神经干细胞系为模型，探讨烟酰胺和烟酰胺抑制素A（TSA）对细胞特性的影响。结果表明，烟酰胺和TSA能明显抑制细胞生长，导致细胞形态改变，并能有效诱导细胞凋亡，且呈剂量依赖性。Western blot分析证实，烟酰胺显着降低bcl-2和p38的表达。进一步深入的分子机制表明，烟酰胺抑制真核生物起始因子4 E结合蛋白1（4 EBP 1）的磷酸化，而TSA则增加bcl-2和p38的表达以及4 EBP 1的磷酸化。然而，烟酰胺和TSA均显著增加细胞色素c（cytc）的表达。这些结果表明，bcl-2、p38、cytc和p-4 EBP 1在组蛋白去乙酰化酶抑制剂烟酰胺和TSA的介导下抑制C17.2神经干细胞的增殖并诱导其凋亡，其作用机制不同。
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 cytochromec(cytc). These results strongly suggest that bcl-2, p38, cytc, 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.