Activation of nerve growth factor synthesis in primary glial cells by phorbol 12-myristate 13-acetate: role of protein kinase C

Activation of nerve growth factor synthesis in primary glial cells by phorbol 12-myristate 13-acetate: role of protein kinase C
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佛波醇 12-肉豆蔻酸酯 13-乙酸酯激活原代胶质细胞中的神经生长因子合成:蛋白激酶 C 的作用

DOI:
10.1016/0006-8993(92)90596-2
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发表时间:
1992
期刊:
影响因子:
2.9
通讯作者:
P. Brachet
P. Brachet
中科院分区:
医学3区
文献类型:
--
作者:
I. Neveu;F. Jehan;R. Houlgatte;D. Wion;P. Brachet

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Phorbol 12-myristate 13-acetate (PMA) induces a dramatic production of nerve growth factor (NGF) in primary cultures of newborn mouse astrocytes maintained in a serum-free medium. This stimulation is dose-dependent and a maximal effect on the levels of cell-secreted factor was observed at a concentration of 10 nM. At this concentration, the promoting effect of PMA appears much more important than that elicited by 10% fetal calf serum (FCS) under the same culture conditions. PMA acts primarily on the accumulation of NGF mRNA, which was detected by northern blot analysis after 6 h of treatment. This accumulation may be totally or partially prevented when PMA-treated glial cells are concommittantly exposed to the protein kinase inhibitors H-7, H-9, and to a lesser degree, HA-1004. The known specificity of these inhibitors agrees with the possibility that protein kinase C (PKC), which constitutes so far the sole known target of PMA, represents a key element involved in the stimulation of NGF gene. The role of PKC is further supported by the observation that α phorbol didecanoate, which has no activity on PKC, is depleted of effect on the synthesis of NGF. Likewise, 1, 2-dioctanoylglycerol (1, 2-DOG) has a weak, but significant promoting action on the production of NGF, unlike the 1, 3-isomer which is not active on PKC. Finally, a treatment of 15 min with 100 nM PMA is sufficient to stimulate the cells, suggesting that the activation phase of PKC, rather than its down regulation, constitutes an important trigger leading to an increased expression of the NGF gene. The effect of PMA and FCS can be reverted, at least in part, by dexamethasone, which depresses the levels of cell-secreted NGF and lowers the pool of NGF transcripts. It is suggested that a balance between activators of PKC and glucocorticoids might control in vivo the expression of NGF synthesis by astrocytes of the central nervous system.
DOI: 10.1126/science.7100931
发表时间: 1982-08
期刊: Science
影响因子: 56.9
作者:
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发表时间: 1989
影响因子: 11.1
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DOI: --
发表时间: 1985
期刊: The Journal of biological chemistry
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DOI: --
发表时间: 1986
期刊: The Journal of biological chemistry
影响因子: --
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