组蛋白去乙酰化酶抑制介导的RGC-5细胞分化及其与存活的相互作用。
Histone deacetylase inhibition-mediated differentiation of RGC-5 cells and interaction with survival.
作者信息
Schwechter Brandon R, Millet Lucia E, Levin Leonard A
机构信息
Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin 53792, USA.
出版信息
Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2845-57. doi: 10.1167/iovs.06-1364.
PURPOSE
The acetylation state of histones is modulated by histone deacetylase (HDAC) and histone acetyltransferase and is an important component in regulating gene transcription, including neuronal differentiation. The authors studied the relationship between histone acetylation and the differentiation and survival of the RGC-5 cell line and compared it with nontranscriptional-dependent differentiation with staurosporine.
METHODS
The retinal ganglion cell line RGC-5 was treated with trichostatin A (TSA), other HDAC inhibitors, and staurosporine; differentiation, neuritogenesis, neurotrophic factor dependence, and dependence on RNA transcription were assessed.
RESULTS
TSA caused significant differentiation and neuritogenesis. Differences between HDAC inhibition and staurosporine differentiation included the proportion of differentiated cells, cell viability, cell morphology, and transcriptional dependence. HDAC inhibition, but not staurosporine differentiation, resulted in RGC-5 cells that were neurotrophic factor dependent.
CONCLUSIONS
These results implicate two different mechanisms for RGC-5 differentiation, with a common downstream effect on neurite outgrowth but a differential effect on neurotrophic factor dependence.
目的
组蛋白的乙酰化状态由组蛋白去乙酰化酶（HDAC）和组蛋白乙酰转移酶调节，并且是调控基因转录（包括神经元分化）的重要组成部分。作者研究了组蛋白乙酰化与RGC - 5细胞系分化和存活之间的关系，并将其与用星形孢菌素进行的非转录依赖性分化进行比较。
方法
用曲古抑菌素A（TSA）、其他HDAC抑制剂和星形孢菌素处理视网膜神经节细胞系RGC - 5；评估分化、神经突形成、神经营养因子依赖性和对RNA转录的依赖性。
结果
TSA引起显著的分化和神经突形成。HDAC抑制与星形孢菌素分化之间的差异包括分化细胞的比例、细胞活力、细胞形态和转录依赖性。HDAC抑制而非星形孢菌素分化导致RGC - 5细胞依赖神经营养因子。
结论
这些结果表明RGC - 5分化存在两种不同机制，对神经突生长有共同的下游效应，但对神经营养因子依赖性有不同效应。
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