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Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells

We previously demonstrated that auraptene (AUR), a natural coumarin derived from citrus plants, exerts anti-inflammatory effects in the brain, resulting in neuroprotection in some mouse models of brain disorders. The present study showed that treatment with AUR significantly increased the release of...

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Autores principales: Furukawa, Yoshiko, Hara, Ryu-ichi, Nakaya, Makiko, Okuyama, Satoshi, Sawamoto, Atsushi, Nakajima, Mitsunari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981972/
https://www.ncbi.nlm.nih.gov/pubmed/31905925
http://dx.doi.org/10.3390/ijms21010253
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author Furukawa, Yoshiko
Hara, Ryu-ichi
Nakaya, Makiko
Okuyama, Satoshi
Sawamoto, Atsushi
Nakajima, Mitsunari
author_facet Furukawa, Yoshiko
Hara, Ryu-ichi
Nakaya, Makiko
Okuyama, Satoshi
Sawamoto, Atsushi
Nakajima, Mitsunari
author_sort Furukawa, Yoshiko
collection PubMed
description We previously demonstrated that auraptene (AUR), a natural coumarin derived from citrus plants, exerts anti-inflammatory effects in the brain, resulting in neuroprotection in some mouse models of brain disorders. The present study showed that treatment with AUR significantly increased the release of glial cell line-derived neurotrophic factor (GDNF), in a dose- and time-dependent manner, by rat C6 glioma cells, which release was associated with increased expression of GDNF mRNA. These results suggest that AUR acted as a neuroprotective agent in the brain via not only its anti-inflammatory action but also its induction of neurotrophic factor. We also showed that (1) the AUR-induced GDNF production was inhibited by U0126, a specific inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) 1/2, and by H89, a specific inhibitor of protein kinase A (PKA); and (2) AUR induced the phosphorylation of cAMP response element-binding protein (CREB), a transcription factor located within the nucleus. These results suggest that AUR-stimulated gdnf gene expression was up-regulated through the PKA/ERK/CREB pathway in C6 cells.
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spelling pubmed-69819722020-02-07 Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells Furukawa, Yoshiko Hara, Ryu-ichi Nakaya, Makiko Okuyama, Satoshi Sawamoto, Atsushi Nakajima, Mitsunari Int J Mol Sci Article We previously demonstrated that auraptene (AUR), a natural coumarin derived from citrus plants, exerts anti-inflammatory effects in the brain, resulting in neuroprotection in some mouse models of brain disorders. The present study showed that treatment with AUR significantly increased the release of glial cell line-derived neurotrophic factor (GDNF), in a dose- and time-dependent manner, by rat C6 glioma cells, which release was associated with increased expression of GDNF mRNA. These results suggest that AUR acted as a neuroprotective agent in the brain via not only its anti-inflammatory action but also its induction of neurotrophic factor. We also showed that (1) the AUR-induced GDNF production was inhibited by U0126, a specific inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) 1/2, and by H89, a specific inhibitor of protein kinase A (PKA); and (2) AUR induced the phosphorylation of cAMP response element-binding protein (CREB), a transcription factor located within the nucleus. These results suggest that AUR-stimulated gdnf gene expression was up-regulated through the PKA/ERK/CREB pathway in C6 cells. MDPI 2019-12-30 /pmc/articles/PMC6981972/ /pubmed/31905925 http://dx.doi.org/10.3390/ijms21010253 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Furukawa, Yoshiko
Hara, Ryu-ichi
Nakaya, Makiko
Okuyama, Satoshi
Sawamoto, Atsushi
Nakajima, Mitsunari
Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells
title Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells
title_full Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells
title_fullStr Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells
title_full_unstemmed Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells
title_short Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells
title_sort citrus auraptene induces glial cell line-derived neurotrophic factor in c6 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981972/
https://www.ncbi.nlm.nih.gov/pubmed/31905925
http://dx.doi.org/10.3390/ijms21010253
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