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Neuregulin-1β regulates tyrosine kinase receptor expression in cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate.
Regul Pept. 2013 Jan 10; 180:33-42.RP

Abstract

Neuregulin-1 (NRG-1) signaling regulates neuronal development, migration, myelination, and synaptic maintenance. Three members of tyrosine kinase receptor (Trk) family, TrkA, TrkB, and TrkC, have been identified in DRG neurons. Whether NRG-1β and its signaling pathways influence the expression of these Trk receptors in DRG neurons is still unclear. In the present study, primary cultured DRG neurons were used to determine the effects of NRG-1β on TrkA, TrkB, and TrkC expression in DRG neurons with excitotoxicity induced by glutamate (Glu). The involvement of phosphatidylinositol 3-kinase (PI3K)/Akt and the effects of extracellular signal-regulated protein kinase (ERK1/2) signaling pathways on NRG-1β were also determined. DRG neurons were cultured for 48h and then exposed to Glu, Glu plus NRG-1β, LY294002 plus Glu plus NRG-1β, PD98059 plus Glu plus NRG-1β, and PD98059 plus LY294002 plus Glu plus NRG-1β for an additional 24h. The DRG neurons were continuously exposed to culture media as a control. After that, all cultures were processed for detection of mRNA levels of TrkA, TrkB, and TrkC using real time-PCR analysis. Protein levels of TrkA, TrkB, and TrkC were detected using a Western blot assay. The expression of TrkA, TrkB, and TrkC in situ was determined by a fluorescent labeling technique. The levels of phosphorylated Akt (pAkt), phosphorylated ERK1/2 (pERK1/2), total protein levels of Akt and ERK1/2 were detected using a Western blot assay. The results indicated that in primary cultured DRG neurons with excitotoxicity induced by Glu, NRG-1β increased the expression of TrkA and TrkB their mRNAs, but not TrkC and its mRNA. Inhibitors (LY294002, PD98059) either alone or in combination blocked the effects of NRG-1β. NRG-1β may play an important role in regulating the expression of different Trk receptors in DRG neurons through the PI3K/Akt and ERK1/2 signaling pathways.

Authors+Show Affiliations

Department of Thoracic Surgery, Shandong University Qilu Hospital, Jinan 250012, China. ywmfy@yahoo.com.cnNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23142316

Citation

Yue, Weiming, et al. "Neuregulin-1β Regulates Tyrosine Kinase Receptor Expression in Cultured Dorsal Root Ganglion Neurons With Excitotoxicity Induced By Glutamate." Regulatory Peptides, vol. 180, 2013, pp. 33-42.
Yue W, Song L, Fu G, et al. Neuregulin-1β regulates tyrosine kinase receptor expression in cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate. Regul Pept. 2013;180:33-42.
Yue, W., Song, L., Fu, G., Li, Y., & Liu, H. (2013). Neuregulin-1β regulates tyrosine kinase receptor expression in cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate. Regulatory Peptides, 180, 33-42. https://doi.org/10.1016/j.regpep.2012.10.005
Yue W, et al. Neuregulin-1β Regulates Tyrosine Kinase Receptor Expression in Cultured Dorsal Root Ganglion Neurons With Excitotoxicity Induced By Glutamate. Regul Pept. 2013 Jan 10;180:33-42. PubMed PMID: 23142316.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuregulin-1β regulates tyrosine kinase receptor expression in cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate. AU - Yue,Weiming, AU - Song,Lijun, AU - Fu,Guangchun, AU - Li,Yizhao, AU - Liu,Huaxiang, Y1 - 2012/11/08/ PY - 2012/05/05/received PY - 2012/09/08/revised PY - 2012/10/17/accepted PY - 2012/11/13/entrez PY - 2012/11/13/pubmed PY - 2013/6/12/medline SP - 33 EP - 42 JF - Regulatory peptides JO - Regul Pept VL - 180 N2 - Neuregulin-1 (NRG-1) signaling regulates neuronal development, migration, myelination, and synaptic maintenance. Three members of tyrosine kinase receptor (Trk) family, TrkA, TrkB, and TrkC, have been identified in DRG neurons. Whether NRG-1β and its signaling pathways influence the expression of these Trk receptors in DRG neurons is still unclear. In the present study, primary cultured DRG neurons were used to determine the effects of NRG-1β on TrkA, TrkB, and TrkC expression in DRG neurons with excitotoxicity induced by glutamate (Glu). The involvement of phosphatidylinositol 3-kinase (PI3K)/Akt and the effects of extracellular signal-regulated protein kinase (ERK1/2) signaling pathways on NRG-1β were also determined. DRG neurons were cultured for 48h and then exposed to Glu, Glu plus NRG-1β, LY294002 plus Glu plus NRG-1β, PD98059 plus Glu plus NRG-1β, and PD98059 plus LY294002 plus Glu plus NRG-1β for an additional 24h. The DRG neurons were continuously exposed to culture media as a control. After that, all cultures were processed for detection of mRNA levels of TrkA, TrkB, and TrkC using real time-PCR analysis. Protein levels of TrkA, TrkB, and TrkC were detected using a Western blot assay. The expression of TrkA, TrkB, and TrkC in situ was determined by a fluorescent labeling technique. The levels of phosphorylated Akt (pAkt), phosphorylated ERK1/2 (pERK1/2), total protein levels of Akt and ERK1/2 were detected using a Western blot assay. The results indicated that in primary cultured DRG neurons with excitotoxicity induced by Glu, NRG-1β increased the expression of TrkA and TrkB their mRNAs, but not TrkC and its mRNA. Inhibitors (LY294002, PD98059) either alone or in combination blocked the effects of NRG-1β. NRG-1β may play an important role in regulating the expression of different Trk receptors in DRG neurons through the PI3K/Akt and ERK1/2 signaling pathways. SN - 1873-1686 UR - https://www.unboundmedicine.com/medline/citation/23142316/Neuregulin_1β_regulates_tyrosine_kinase_receptor_expression_in_cultured_dorsal_root_ganglion_neurons_with_excitotoxicity_induced_by_glutamate_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0167-0115(12)00246-7 DB - PRIME DP - Unbound Medicine ER -