Yusta B, Ortiz-Caro J, Pascual A, Aranda A
Unidad de Endocrinologia Experimental, CSIC, Facultad de Medicina, Universidad Autonoma, Madrid, Spain.
J Neurochem. 1988 Dec;51(6):1808-18. doi: 10.1111/j.1471-4159.1988.tb01162.x.
We 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 H1(0), a protein that increases in neuroblastoma cells as a result of different treatments that block cell division. The concentration of H1(0) 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 cyclic nucleotide itself.
我们比较了福斯可林、N6,2'-O-二丁酰腺苷3':5'-环磷酸单酯（二丁酰环磷酸腺苷，Bt2-cAMP）和丁酸盐对神经母细胞瘤细胞生理学多个方面的影响。用福斯可林和Bt2-cAMP孵育后，Neuro 2A细胞的形态相似，二者均能引起广泛的神经突生长，而在丁酸盐存在的情况下，虽形成了一些初级神经突，但并不那么广泛。所有化合物均产生剂量依赖性的细胞增殖抑制作用，但Bt2-cAMP的作用比福斯可林更显著，这表明Bt2-cAMP的作用部分归因于释放出的丁酸盐。与用丁酸盐或Bt2-cAMP孵育的细胞相比，未处理细胞或用福斯可林处理的细胞中的乙酰胆碱酯酶活性更低。这表明环磷酸腺苷在该酶的调节中不起作用。Bt2-cAMP可导致组蛋白乙酰化，这是丁酸盐在培养细胞中的一种众所周知的作用，而福斯可林不影响这种修饰。因此，甲状腺激素受体（一种核蛋白，其浓度通过染色质蛋白乙酰化的变化由丁酸盐调节）的水平在与Bt2-cAMP或丁酸盐孵育的细胞中降低，但不受福斯可林影响。丁酸盐提高了组蛋白H1(0)的浓度，在神经母细胞瘤细胞中，由于不同的阻断细胞分裂的处理，该蛋白会增加。用Bt2-cAMP处理的细胞中H1(0)的浓度处于用丁酸盐和福斯可林处理后所发现的水平之间。目前的结果清楚地表明，Bt2-cAMP对神经母细胞瘤细胞的某些作用可归因于该化合物的丁酰部分，而非环核苷酸本身。
