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Hindi Research Article
Genomic Control of Upregulation of GRP78 Expression for Promotion of Neurite Elongation and Attenuation of Cell Death via PKA-Mediated Signaling in PC12 Cells
| Ryosuke Yamazoe1, Yoshiki Nishihata2, Kazuma Nakagawa2, Hiroki Aoyama2 and Koji Shimoke1,2* | |
| 1High Technology Research Core (HRC), Kansai University, 3-3-35, Yamate-cho, Suita, Osaka 564-8680, Japan | |
| 2Laboratory of Neurobiology, Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35, Yamate-cho, Suita, Osaka 564-8680, Japan | |
| Corresponding Author : | Koji Shimoke Laboratory of Neurobiology Department of Life Science and Biotechnology Faculty of Chemistry, Materials and Bioengineering Kansai University, 3-3-35, Yamate-cho Suita, Osaka 564-8680, Japan Tel: +81-6-6368-0853 Fax: +81-6-6330-3770 E-mail: shimoke@kansai-u.ac.jp |
| Received October 08, 2015; Accepted November 17, 2015; Published November 23, 2015 | |
| Citation: Yamazoe R, Nishihata Y, Nakagawa K, Aoyama H, Shimoke K (2015) Genomic Control of Upregulation of GRP78 Expression for Promotion of Neurite Elongation and Attenuation of Cell Death via PKA-Mediated Signaling in PC12 Cells. Clin Pharmacol Biopharm 4:150. doi:10.4172/2167-065X.1000150 | |
| Copyright: © 2015 Yamazoe R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |
Abstract
Neurodegeneration occurs due to neuronal cell death and subsequently disrupts neuronal networks. In current medicine, methods for interruption of neuronal cell death and avoidance of disruption of neuronal networks have potential as therapy for neurodegenerative disorders. Development of this therapy requires analysis of the molecular mechanism of neurite extension that leads to network formation. Here, we show that forskolin (fsk), an activator of adenylate cyclase, increases the intracellular cAMP concentration and induces neurite outgrowth in PC12 cells. The effect of fsk on neurite outgrowth was diminished by H89, an inhibitor of protein kinase A (PKA), and by PD98059 and U0126, which are inhibitors of the mitogen-activated protein kinase (MAPK) signaling pathway. With fsk treatment in the presence of tunicamycin, an inducer of cell death, the activity of the glucose-regulated protein 78 (GRP78) promoters was upregulated. Interestingly, this effect was completely abolished by H89 and by PD98059 and U0126. This phenomenon was confirmed using a dominant-negative PKA-expressing PC12 cell line, in which the PKA-mediated signaling pathway was completely eliminated. These lines of evidence suggest that GRP78 promotes neuronal elongation that is regulated by fsk and mediated by PKA.
