Abstract:
:The rat pheochromocytoma PC12 cell line has been an invaluable model system for studying neuritogenesis. Nerve growth factor (NGF) elicits multiple aspects of neurite outgrowth in PC12 cells. It is therefore difficult to dissect and assign an individual signaling pathway to each stage of neuritogenesis. We have recently reported the isolation of a variant PC12 cell line, PC12-N1 (N1), which spontaneously extends neuritic processes and exhibits an increased sensitivity to NGF. Here, we show that, under different culture conditions, the cells display three distinct phases of neuritogenesis consisting of neurite initiation, rapid neurite elongation, and a maturation process characterized by the thickening of neurites and increase in cell soma sizes. We demonstrate that signaling through ERK, but not p38 or JNK, is required for the spontaneous neurite initiation and extension. Treatment with low concentrations of NGF induces rapid neurite elongation without affecting neurite branching and cell soma sizes. Such a rapid neurite outgrowth can be blocked by the inhibition of ERK, but not JNK, activities. In the presence of higher concentrations of NGF, the N1 cells undergo further differentiation with many characteristics of mature neurons in culture, e.g. larger cell soma and numerous branches/connections. This process can be completely blocked by inhibiting ERK or JNK activities using specific inhibitors. These results suggest that ERK and JNK signals play different roles in neuritogenesis, and that JNK activity is essential in the late stages of neuritogenesis. Furthermore, our results demonstrate that signaling dosage is important in the activation of a specific pathway, leading to distinctive biological outcomes.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Xiao J,Liu Ydoi
10.1046/j.1471-4159.2003.01961.xkeywords:
subject
Has Abstractpub_date
2003-09-01 00:00:00pages
1516-23issue
6eissn
0022-3042issn
1471-4159pii
1961journal_volume
86pub_type
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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更新日期:1999-05-01 00:00:00
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journal_title:Journal of neurochemistry
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更新日期:1995-12-01 00:00:00
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journal_title:Journal of neurochemistry
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doi:10.1046/j.1471-4159.2001.00159.x
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.0720835.x
更新日期:1999-02-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2009.06485.x
更新日期:2010-01-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1983-11-01 00:00:00
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更新日期:1992-02-01 00:00:00
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journal_title:Journal of neurochemistry
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更新日期:2012-03-01 00:00:00
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更新日期:2020-08-01 00:00:00
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journal_title:Journal of neurochemistry
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更新日期:2019-02-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
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更新日期:2010-09-01 00:00:00
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journal_title:Journal of neurochemistry
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pub_type: 杂志文章
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更新日期:2008-08-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1046/j.1471-4159.1999.0732227.x
更新日期:1999-12-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb07148.x
更新日期:1985-01-01 00:00:00
abstract::After traumatic brain injury, progesterone has important neuroprotective effects in the nervous system. There is better functional outcome and less oedema formation in pseudopregnant rat females (high levels of endogenous progesterone) than in males. In addition to intracellular progesterone receptors, membrane bindin...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2005.03127.x
更新日期:2005-06-01 00:00:00