Cyclic AMP, but not basic FGF, increases the in vitro survival of mesencephalic dopaminergic neurons and protects them from MPP+‐induced degeneration
Cyclic AMP, but not basic FGF, increases the in vitro survival of mesencephalic dopaminergic neurons and protects them from MPP+‐induced degeneration
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环 AMP（而非碱性 FGF）可增加中脑多巴胺能神经元的体外存活率，并保护它们免受 MPP+ 诱导的变性
DOI：
10.1002/jnr.490320208
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发表时间：
1992
影响因子：
4.2
通讯作者：
C. Basel
中科院分区：
文献类型：
--
作者：
J. Hartikka;M. Staufenbiel;H. Lubbert;P. Research;I. Room;Sandoz Pharma;C. Basel
我们研究了蛋白激酶C和cAMP依赖性蛋白激酶的刺激如何影响胚胎E14天胎鼠原代细胞培养物中中脑多巴胺能神经元的发育。将激活这些第二信使系统的化合物的作用与碱性成纤维细胞生长因子（bFGF）和胰岛素样生长因子I（IGF-I）的作用进行比较。在中脑文化，有一个连续的损失多巴胺能神经元。尽管这种细胞数量的下降，神经递质摄取每神经元随时间增加，表明幸存的多巴胺能神经元继续其生化分化，而其他退化。IGF-I和bFGF不影响多巴胺能神经元的数量。然而，在bFGF和IGF-I处理的培养物中，每个神经元的多巴胺摄取显著更高，表明这些因素刺激了分化。蛋白激酶C和cAMP依赖性蛋白激酶不参与介导bFGF和IGF-I的作用。用佛波醇酯处理培养物不影响多巴胺摄取，而细胞内cAMP水平升高导致多巴胺摄取增加，这与bFGF或IGF-I引起的多巴胺摄取是相加的。进一步的分析表明，暴露中脑培养物的双丁酰cAMP（dbcAMP）在第一个3天后，增加多巴胺能神经元的存活，而长期治疗衰减的多巴胺摄取系统的发展。此外，cAMP，而不是bFGF，能够防止由1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）的活性代谢产物1-甲基-4-苯基-吡啶离子（MPP+）诱导的多巴胺能神经元的变性。结果表明，增加细胞内cAMP水平保护多巴胺能神经元的情况下，如解离和电镀或暴露于神经毒性化合物的过程中的压力。我们的研究结果揭示了治疗帕金森病的新的可能性。© 1992 Wiley利斯公司
We studied how stimulation of protein kinase C and cAMP‐dependent protein kinases affect the development of mesencephalic dopaminergic neurons in primary cell cultures derived from fetal rats at embryonic day E14. The effects of compounds which activate these second messenger systems were compared to those of basic fibroblast growth factor (bFGF) and insulin‐like growth factor I (IGF‐I). In mesencephalic cultures, there was a continuous loss of dopaminergic neurons. Despite this decline in cell number, neurotransmitter uptake per neuron increased with time, indicating that the surviving dopaminergic neurons continued their biochemical differentiation while others degenerated. IGF‐I and bFGF did not affect the number of dopaminergic neurons. However, dopamine uptake per neuron was significantly higher in bFGF and IGF‐I treated cultures, suggesting that these factors stimulated differentiation. Protein kinase C and cAMP‐dependent protein kinases were not involved in mediating the effects of bFGF and IGF‐I. Treatment of cultures with phorbol esters did not affect dopamine uptake, whereas elevated levels of intracellular cAMP resulted in an increase in dopamine uptake which was additive to that elicited by bFGF or IGF‐I. Further analysis revealed that exposure of mesencephalic cultures to dibutyryl cAMP (dbcAMP) during the first 3 days after plating increased the survival of dopaminergic neurons, whereas prolonged treatment attenuated the development of the dopamine uptake system. Moreover, cyclic AMP, but not bFGF, was able to prevent the degeneration of dopaminergic neurons induced by 1‐methyl‐4‐phenyl‐pyridinium ion (MPP+), the active metabolite of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). The results suggest that increased intracellular levels of cAMP protect dopaminergic neurons in situations of stress like the process of dissociation and plating or the exposure to neurotoxic compounds. Our results reveal novel possibilities for the treatment of Parkinson's disease. © 1992 Wiley‐Liss, Inc.
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影响因子：
13.9
作者：
R. Zigmond;M. Schwarzschild;A. Rittenhouse
通讯作者：
R. Zigmond;M. Schwarzschild;A. Rittenhouse
影响因子：
2.9
作者：
P. Walicke;A. Baird
通讯作者：
P. Walicke;A. Baird
影响因子：
56.9
作者：
LEE, PL;JOHNSON, DE;WILLIAMS, LT
通讯作者：
WILLIAMS, LT
(Rp)-和(Sp)-腺苷环3,5-硫代磷酸酯与II型牛心肌腺苷环3,5-磷酸依赖性蛋白激酶相互作用的动力学研究。
影响因子：
2.9
作者：
O'Brian,CA;Roczniak,SO;Bramson,HN;Baraniak,J;Stec,WJ;Kaiser,ET
通讯作者：
Kaiser,ET
碱性成纤维细胞生长因子神经元受体的表征以及与间充质细胞受体的比较。
DOI：
--
发表时间：
1989
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Walicke,PA;Feige,JJ;Baird,A
通讯作者：
Baird,A