Histone deacetylase inhibition-mediated differentiation of RGC-5 cells and interaction with survival.
OBJECTIVE
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.
Schwechter
Brandon R
BR
Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin 53792, USA.
Millet
Lucia E
LE
Levin
Leonard A
LA
D000107:Acetylation; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000502:physiology; D051381:Rats; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000201:enzymology; D019311:Staurosporine / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D009414:Nerve Growth Factors; C085348:tau-1 monoclonal antibody; C012589:trichostatin A; D019311:Staurosporine