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Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants

Extracellular signal-regulated kinases 1/2 (ERK1/2), components of the mitogen-activated protein kinase (MAPK) signaling cascade, have been recently shown to be involved in synaptic plasticity and in the development of long-term memory in the central nervous system (CNS). We therefore examined the a...

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Autores principales: Furukawa, Yoshiko, Okuyama, Satoshi, Amakura, Yoshiaki, Watanabe, Sono, Fukata, Takahiro, Nakajima, Mitsunari, Yoshimura, Morio, Yoshida, Takashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291996/
https://www.ncbi.nlm.nih.gov/pubmed/22408427
http://dx.doi.org/10.3390/ijms13021832
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author Furukawa, Yoshiko
Okuyama, Satoshi
Amakura, Yoshiaki
Watanabe, Sono
Fukata, Takahiro
Nakajima, Mitsunari
Yoshimura, Morio
Yoshida, Takashi
author_facet Furukawa, Yoshiko
Okuyama, Satoshi
Amakura, Yoshiaki
Watanabe, Sono
Fukata, Takahiro
Nakajima, Mitsunari
Yoshimura, Morio
Yoshida, Takashi
author_sort Furukawa, Yoshiko
collection PubMed
description Extracellular signal-regulated kinases 1/2 (ERK1/2), components of the mitogen-activated protein kinase (MAPK) signaling cascade, have been recently shown to be involved in synaptic plasticity and in the development of long-term memory in the central nervous system (CNS). We therefore examined the ability of Citrus compounds to activate ERK1/2 in cultured rat cortical neurons, whose activation might have a protective effect against neurodegenerative neurological disorders. Among the samples tested, extracts prepared from the peels of Citrus grandis (Kawachi bankan) were found to have the greatest ability to activate ERK1/2. The active substances were isolated by chromatographic separation, and one of them was identified to be 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF). HMF significantly induced the phosphorylation of cAMP response element-binding protein (CREB), a downstream target of activated ERK1/2, which appears to be a critical step in the signaling cascade for the structural changes underlying the development of long-term potentiation (LTP). In addition, the administration of HMF into mice treated with NMDA receptor antagonist MK-801 restored the MK-801-induced deterioration of spatial learning performance in the Morris mater-maze task. Taken together, these results suggest that HMF is a neurotrophic agent for treating patients with memory disorders.
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spelling pubmed-32919962012-03-09 Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants Furukawa, Yoshiko Okuyama, Satoshi Amakura, Yoshiaki Watanabe, Sono Fukata, Takahiro Nakajima, Mitsunari Yoshimura, Morio Yoshida, Takashi Int J Mol Sci Article Extracellular signal-regulated kinases 1/2 (ERK1/2), components of the mitogen-activated protein kinase (MAPK) signaling cascade, have been recently shown to be involved in synaptic plasticity and in the development of long-term memory in the central nervous system (CNS). We therefore examined the ability of Citrus compounds to activate ERK1/2 in cultured rat cortical neurons, whose activation might have a protective effect against neurodegenerative neurological disorders. Among the samples tested, extracts prepared from the peels of Citrus grandis (Kawachi bankan) were found to have the greatest ability to activate ERK1/2. The active substances were isolated by chromatographic separation, and one of them was identified to be 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF). HMF significantly induced the phosphorylation of cAMP response element-binding protein (CREB), a downstream target of activated ERK1/2, which appears to be a critical step in the signaling cascade for the structural changes underlying the development of long-term potentiation (LTP). In addition, the administration of HMF into mice treated with NMDA receptor antagonist MK-801 restored the MK-801-induced deterioration of spatial learning performance in the Morris mater-maze task. Taken together, these results suggest that HMF is a neurotrophic agent for treating patients with memory disorders. Molecular Diversity Preservation International (MDPI) 2012-02-09 /pmc/articles/PMC3291996/ /pubmed/22408427 http://dx.doi.org/10.3390/ijms13021832 Text en © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Furukawa, Yoshiko
Okuyama, Satoshi
Amakura, Yoshiaki
Watanabe, Sono
Fukata, Takahiro
Nakajima, Mitsunari
Yoshimura, Morio
Yoshida, Takashi
Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants
title Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants
title_full Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants
title_fullStr Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants
title_full_unstemmed Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants
title_short Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants
title_sort isolation and characterization of activators of erk/mapk from citrus plants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291996/
https://www.ncbi.nlm.nih.gov/pubmed/22408427
http://dx.doi.org/10.3390/ijms13021832
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