دورية أكاديمية
Nogo-p4 Suppresses TrkA Signaling Induced by Low Concentrations of Nerve Growth Factor Through NgR1 in Differentiated PC12 Cells
| العنوان: | Nogo-p4 Suppresses TrkA Signaling Induced by Low Concentrations of Nerve Growth Factor Through NgR1 in Differentiated PC12 Cells |
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| المؤلفون: | You-Ming Fan, Qing-Yuan Huang, Yin-Ai Wu, Alan R. Harvey, Qi Cui, Yu-Qi Gao |
| المصدر: | Neurosignals, Vol 24, Iss 1, Pp 25-39 (2016) |
| بيانات النشر: | Cell Physiol Biochem Press GmbH & Co KG, 2016. |
| سنة النشر: | 2016 |
| المجموعة: | LCC:Neurology. Diseases of the nervous system LCC:Neurophysiology and neuropsychology |
| مصطلحات موضوعية: | TrkA signaling, p75, PC12 cells, Nogo receptor 1 (NgR1), Nogo-p4, Nerve growth factor (NGF), Neurology. Diseases of the nervous system, RC346-429, Neurophysiology and neuropsychology, QP351-495 |
| الوصف: | Background: Regeneration of injured axons in adult mammalian central nervous system (CNS) is not spontaneous. Nogo is a major inhibitory molecule contributing to axon regeneration failure. The molecular mechanisms of Nogo inhibition of axon regeneration are not completely understood. To further investigate the underlying mechanisms, we studied the effects of Nogo-p4, a 25-amino acid core inhibitory fragment of Nogo, on nerve growth factor (NGF)-induced TrkA signaling. Methods: NGF-differentiated PC12 cells were used as cell models. The effects of Nogo-p4 on two key components of TrkA signaling, phosphorylated Erk1/2 and Akt, were analyzed by western blot. Co-immunoprecipitation experiments were performed to detect the formation of NgR1/p75 complexes. Neurite growth was quantified by measuring the neurite length. Results: Nogo-p4 did not significantly affect TrkA signaling induced by 100 ng/ml NGF, but signaling was suppressed when an NGF concentration of 5 ng/ml was used. Further investigation demonstrated that Nogo-p4 affected TrkA signaling in an NGF concentration-dependent manner. Nogo-p4 suppression of TrkA signaling was strong at low (1 and 5 ng/ml), moderate at intermediate (25 ng/ml), but absent at high (50 and 100 ng/ml) NGF concentrations. NEP1-40 attenuated, and NgR1 overexpression enhanced, Nogo-p4 suppression of TrkA signaling induced by low concentrations of NGF. High but not low concentrations of NGF reduced the formation of NgR1/p75 complexes triggered by Nogo-p4. Nogo-p4 strongly inhibited neurite growth induced by low rather than high concentrations of NGF. Conclusion: Nogo-p4 binding with NgR1 suppresses TrkA signaling induced by low concentrations of NGF in differentiated PC12 cells. Suppression of NGF-induced TrkA signaling may be another mechanism by which Nogo inhibits neurite growth. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1424-862X 1424-8638 |
| Relation: | http://www.karger.com/Article/FullText/442609; https://doaj.org/toc/1424-862X; https://doaj.org/toc/1424-8638 |
| DOI: | 10.1159/000442609 |
| URL الوصول: | https://doaj.org/article/70793282f1444d56aecc6bb441f943fb |
| رقم الأكسشن: | edsdoj.70793282f1444d56aecc6bb441f943fb |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 1424862X 14248638 |
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| DOI: | 10.1159/000442609 |