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Luteolin Induces microRNA-132 Expression and Modulates Neurite Outgrowth in PC12 Cells

Luteolin (3′,4′,5,7-tetrahydroxyflavone), a food-derived flavonoid, has been reported to exert neurotrophic properties that are associated with its capacity to promote neuronal survival and neurite outgrowth. In this study, we report for the first time that luteolin induces the persistent expression...

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Autores principales: Lin, Lian-Fang, Chiu, Szu-Ping, Wu, Ming-Jiuan, Chen, Pei-Yi, Yen, Jui-Hung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420912/
https://www.ncbi.nlm.nih.gov/pubmed/22916239
http://dx.doi.org/10.1371/journal.pone.0043304
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author Lin, Lian-Fang
Chiu, Szu-Ping
Wu, Ming-Jiuan
Chen, Pei-Yi
Yen, Jui-Hung
author_facet Lin, Lian-Fang
Chiu, Szu-Ping
Wu, Ming-Jiuan
Chen, Pei-Yi
Yen, Jui-Hung
author_sort Lin, Lian-Fang
collection PubMed
description Luteolin (3′,4′,5,7-tetrahydroxyflavone), a food-derived flavonoid, has been reported to exert neurotrophic properties that are associated with its capacity to promote neuronal survival and neurite outgrowth. In this study, we report for the first time that luteolin induces the persistent expression of microRNA-132 (miR-132) in PC12 cells. The correlation between miR-132 knockdown and a decrease in luteolin-mediated neurite outgrowth may indicate a mechanistic link by which miR-132 functions as a mediator for neuritogenesis. Furthermore, we find that luteolin led to the phosphorylation and activation of cAMP response element binding protein (CREB), which is associated with the up-regulation of miR-132 and neurite outgrowth. Moreover, luteolin-induced CREB activation, miR-132 expression and neurite outgrowth were inhibited by adenylate cyclase, protein kinase A (PKA) and MAPK/ERK kinase 1/2 (MEK1/2) inhibitors but not by protein kinase C (PKC) or calcium/calmodulin-dependent protein kinase II (CaMK II) inhibitors. Consistently, we find that luteolin treatment increases ERK phosphorylation and PKA activity in PC12 cells. These results show that luteolin induces the up-regulation of miR-132, which serves as an important regulator for neurotrophic actions, mainly acting through the activation of cAMP/PKA- and ERK-dependent CREB signaling pathways in PC12 cells.
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spelling pubmed-34209122012-08-22 Luteolin Induces microRNA-132 Expression and Modulates Neurite Outgrowth in PC12 Cells Lin, Lian-Fang Chiu, Szu-Ping Wu, Ming-Jiuan Chen, Pei-Yi Yen, Jui-Hung PLoS One Research Article Luteolin (3′,4′,5,7-tetrahydroxyflavone), a food-derived flavonoid, has been reported to exert neurotrophic properties that are associated with its capacity to promote neuronal survival and neurite outgrowth. In this study, we report for the first time that luteolin induces the persistent expression of microRNA-132 (miR-132) in PC12 cells. The correlation between miR-132 knockdown and a decrease in luteolin-mediated neurite outgrowth may indicate a mechanistic link by which miR-132 functions as a mediator for neuritogenesis. Furthermore, we find that luteolin led to the phosphorylation and activation of cAMP response element binding protein (CREB), which is associated with the up-regulation of miR-132 and neurite outgrowth. Moreover, luteolin-induced CREB activation, miR-132 expression and neurite outgrowth were inhibited by adenylate cyclase, protein kinase A (PKA) and MAPK/ERK kinase 1/2 (MEK1/2) inhibitors but not by protein kinase C (PKC) or calcium/calmodulin-dependent protein kinase II (CaMK II) inhibitors. Consistently, we find that luteolin treatment increases ERK phosphorylation and PKA activity in PC12 cells. These results show that luteolin induces the up-regulation of miR-132, which serves as an important regulator for neurotrophic actions, mainly acting through the activation of cAMP/PKA- and ERK-dependent CREB signaling pathways in PC12 cells. Public Library of Science 2012-08-16 /pmc/articles/PMC3420912/ /pubmed/22916239 http://dx.doi.org/10.1371/journal.pone.0043304 Text en © 2012 Lin et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Lin, Lian-Fang
Chiu, Szu-Ping
Wu, Ming-Jiuan
Chen, Pei-Yi
Yen, Jui-Hung
Luteolin Induces microRNA-132 Expression and Modulates Neurite Outgrowth in PC12 Cells
title Luteolin Induces microRNA-132 Expression and Modulates Neurite Outgrowth in PC12 Cells
title_full Luteolin Induces microRNA-132 Expression and Modulates Neurite Outgrowth in PC12 Cells
title_fullStr Luteolin Induces microRNA-132 Expression and Modulates Neurite Outgrowth in PC12 Cells
title_full_unstemmed Luteolin Induces microRNA-132 Expression and Modulates Neurite Outgrowth in PC12 Cells
title_short Luteolin Induces microRNA-132 Expression and Modulates Neurite Outgrowth in PC12 Cells
title_sort luteolin induces microrna-132 expression and modulates neurite outgrowth in pc12 cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420912/
https://www.ncbi.nlm.nih.gov/pubmed/22916239
http://dx.doi.org/10.1371/journal.pone.0043304
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