Cyclic AMP increases the survival of ganglion cells in mixed retinal cell cultures in the absence of exogenous neurotrophic molecules, an effect that involves cholinergic activity
Cyclic AMP increases the survival of ganglion cells in mixed retinal cell cultures in the absence of exogenous neurotrophic molecules, an effect that involves cholinergic activity
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DOI：
10.1590/s0100-879x2001001200011
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发表时间：
2001-12-01
影响因子：
2.3
通讯作者：
Araujo, EG
中科院分区：
文献类型：
--
作者：
Santos, RCC;Araujo, EG
自然细胞死亡是神经系统发育过程中发生的一种众所周知的退行性现象。由靶细胞和传入细胞以及神经胶质细胞产生的营养分子的作用已被广泛证实。文献数据表明，cAMP可以调节神经元细胞的存活。用毛喉素（一种腺苷酸环化酶的激活剂）处理混合视网膜细胞培养物48小时。结果表明，50 μ M毛喉素诱导的视网膜神经节细胞（RGC）的存活率增加了两倍，在没有外源性营养因子。这种作用是剂量依赖性的，并被1 μ M H89消除（蛋白激酶A抑制剂），1.25 μ M氯化白屈菜红碱（蛋白激酶C抑制剂），50 μ M PD 98059（MEK的抑制剂），25 μ M Ly 294002（磷脂酰肌醇-3激酶抑制剂），30 nM布雷菲德菌素A（多肽释放抑制剂）和10 μ M染料木黄酮或1 ng/ml除莠霉素（酪氨酸激酶抑制剂）。10 μ M阿托品或1 μ M替仑西平对毒蕈碱受体的抑制作用也阻断了毛喉素的作用。当我们使用25 μ M BAPTA（一种细胞内钙螯合剂）以及20 μ M 5-氟-2 '-脱氧尿苷（一种细胞增殖抑制剂）时，我们也消除了这种效应。我们的研究结果表明，cAMP起着重要的作用，控制RGCs的生存。这种作用直接依赖于M1受体活化，表明胆碱能活性介导RGC存活的增加。我们提出了一个模型，其中涉及胆碱能无长突细胞和神经胶质细胞在增加RGC生存引起的毛喉素治疗。
Natural cell death is a well-known degenerative phenomenon occurring during development of the nervous system. The role of trophic molecules produced by target and afferent cells as well as by glial cells has been extensively demonstrated. Literature data demonstrate that cAMP can modulate the survival of neuronal cells. Cultures of mixed retinal cells were treated with forskolin (an activator of the enzyme adenylyl cyclase) for 48 h. The results show that 50 muM forskolin induced a two-fold increase in the survival of retinal ganglion cells (RGCs) in the absence of exogenous trophic factors. This effect was dose dependent and abolished by 1 muM H89 (an inhibitor of protein kinase A), 1.25 muM chelerythrine chloride (an inhibitor of protein kinase C), 50 muM PD 98059 (an inhibitor of MEK), 25 muM Ly 294002 (an inhibitor of phosphatidylinositol-3 kinase), 30 nM brefeldin A (an inhibitor of polypeptide release), and 10 muM genistein or 1 ng/ml herbimycin (inhibitors of tyrosine kinase enzymes). The inhibition of muscarinic receptors by 10 muM atropine or 1 muM telenzepine also blocked the effect of forskolin. When we used 25 muM BAPTA, an intracellular calcium chelator, as well as 20 muM 5-fluoro-2'-deoxy-uridine, an inhibitor of cell proliferation, we also abolished the effect. Our results indicate that cAMP plays an important role controlling the survival of RGCs. This effect is directly dependent on M1 receptor activation indicating that cholinergic activity mediates the increase in RGC survival. We propose a model which involves cholinergic amacrine cells and glial cells in the increase of RGC survival elicited by forskolin treatment.