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Title

Comparison of the effects of forskolin and dibutyryl cyclic AMP in neuroblastoma cells: Evidence that some of the actions of dibutyryl cyclic AMP are mediated by butyrate

AuthorsYusta, Bernardo; Ortiz-Caro, Javier; Pascual, Ángel ; Aranda, Ana
Issue Date1988
PublisherWiley-Blackwell
CitationJournal of Neurochemistry 51(6): 1808-1818 (1988)
AbstractWe have compared the effects of forskolin, N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (dibutyryl cyclic AMP, Bt2-cAMP), and butyrate on several aspects of neuroblastoma cell physiology. The morphology of Neuro 2A cells was similar after incubation with forskolin and Bt2-cAMP, which caused extensive neurite outgrowth, whereas in the presence of butyrate some rudimentary neurites were formed but they were not nearly as extensive. All compounds produced a dose-dependent inhibition of cell proliferation, but the effect of Bt2-cAMP was more marked than that caused by forskolin, thus showing that the effect of Bt2-cAMP is due partially to the butyrate released. Acetylcholinesterase activity was lower in the cells incubated with butyrate or Bt2-cAMP than in untreated cells or in forskolin-treated cells. This suggests that cyclic AMP does not play a role in the regulation of this enzyme. Bt2-cAMP produced histone acetylation, a well-known effect of butyrate in cultured cells, whereas forskolin did not affect this modification. Consequently, the levels of thyroid hormone receptor, a nuclear protein whose concentration is regulated by butyrate through changes in acetylation of chromatin proteins, were decreased in cells incubated with Bt2-cAMP or butyrate, but were unaffected by forskolin. Butyrate elevated the concentration of histone H10, a protein that increases in neuroblastoma cells as a result of different treatments that block cell division. The concentration of H10 in the cells treated with Bt2-cAMP was at a level intermediate between that found after treatment with butyrate and with forskolin. The present results clearly indicate that some of the effects of Bt2-cAMP on neuroblastoma cells can be attributed to the butyryl moiety of this compound rather than to the cylic nucleotide itself.
URIhttp://hdl.handle.net/10261/78731
DOI10.1111/j.1471-4159.1988.tb01162.x
Identifiersdoi: 10.1111/j.1471-4159.1988.tb01162.x
issn: 0022-3042
e-issn: 1471-4159
Appears in Collections:(IIBM) Artículos
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