A novel target of action of minocycline in NGF-induced neurite outgrowth in PC12 cells: translation initiation [corrected] factor eIF4AI.

<h4>Background</h4>Minocycline, a second-generation tetracycline antibiotic, has potential activity for the treatment of several neurodegenerative and psychiatric disorders. However, its mechanisms of action remain to be determined.<h4>Methodology/principal findings</h4>We fo...

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Autores principales:	Kenji Hashimoto, Tamaki Ishima
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/58eb4390d42b46a3809893401d46d9e8
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spelling	oai:doaj.org-article:58eb4390d42b46a3809893401d46d9e82021-11-18T07:02:22ZA novel target of action of minocycline in NGF-induced neurite outgrowth in PC12 cells: translation initiation [corrected] factor eIF4AI.1932-620310.1371/journal.pone.0015430https://doaj.org/article/58eb4390d42b46a3809893401d46d9e82010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21151481/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Minocycline, a second-generation tetracycline antibiotic, has potential activity for the treatment of several neurodegenerative and psychiatric disorders. However, its mechanisms of action remain to be determined.<h4>Methodology/principal findings</h4>We found that minocycline, but not tetracycline, significantly potentiated nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells, in a concentration dependent manner. Furthermore, we found that the endoplasmic reticulum protein inositol 1,4,5-triphosphate (IP3) receptors and several common signaling molecules (PLC-γ, PI3K, Akt, p38 MAPK, c-Jun N-terminal kinase (JNK), mammalian target of rapamycin (mTOR), and Ras/Raf/ERK/MAPK pathways) might be involved in the active mechanism of minocycline. Moreover, we found that a marked increase of the eukaryotic translation initiation factor eIF4AI protein by minocycline, but not tetracycline, might be involved in the active mechanism for NGF-induced neurite outgrowth.<h4>Conclusions/significance</h4>These findings suggest that eIF4AI might play a role in the novel mechanism of minocycline. Therefore, agents that can increase eIF4AI protein would be novel therapeutic drugs for certain neurodegenerative and psychiatric diseases.Kenji HashimotoTamaki IshimaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 11, p e15430 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kenji Hashimoto Tamaki Ishima A novel target of action of minocycline in NGF-induced neurite outgrowth in PC12 cells: translation initiation [corrected] factor eIF4AI.
description	<h4>Background</h4>Minocycline, a second-generation tetracycline antibiotic, has potential activity for the treatment of several neurodegenerative and psychiatric disorders. However, its mechanisms of action remain to be determined.<h4>Methodology/principal findings</h4>We found that minocycline, but not tetracycline, significantly potentiated nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells, in a concentration dependent manner. Furthermore, we found that the endoplasmic reticulum protein inositol 1,4,5-triphosphate (IP3) receptors and several common signaling molecules (PLC-γ, PI3K, Akt, p38 MAPK, c-Jun N-terminal kinase (JNK), mammalian target of rapamycin (mTOR), and Ras/Raf/ERK/MAPK pathways) might be involved in the active mechanism of minocycline. Moreover, we found that a marked increase of the eukaryotic translation initiation factor eIF4AI protein by minocycline, but not tetracycline, might be involved in the active mechanism for NGF-induced neurite outgrowth.<h4>Conclusions/significance</h4>These findings suggest that eIF4AI might play a role in the novel mechanism of minocycline. Therefore, agents that can increase eIF4AI protein would be novel therapeutic drugs for certain neurodegenerative and psychiatric diseases.
format	article
author	Kenji Hashimoto Tamaki Ishima
author_facet	Kenji Hashimoto Tamaki Ishima
author_sort	Kenji Hashimoto
title	A novel target of action of minocycline in NGF-induced neurite outgrowth in PC12 cells: translation initiation [corrected] factor eIF4AI.
title_short	A novel target of action of minocycline in NGF-induced neurite outgrowth in PC12 cells: translation initiation [corrected] factor eIF4AI.
title_full	A novel target of action of minocycline in NGF-induced neurite outgrowth in PC12 cells: translation initiation [corrected] factor eIF4AI.
title_fullStr	A novel target of action of minocycline in NGF-induced neurite outgrowth in PC12 cells: translation initiation [corrected] factor eIF4AI.
title_full_unstemmed	A novel target of action of minocycline in NGF-induced neurite outgrowth in PC12 cells: translation initiation [corrected] factor eIF4AI.
title_sort	novel target of action of minocycline in ngf-induced neurite outgrowth in pc12 cells: translation initiation [corrected] factor eif4ai.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/58eb4390d42b46a3809893401d46d9e8
work_keys_str_mv	AT kenjihashimoto anoveltargetofactionofminocyclineinngfinducedneuriteoutgrowthinpc12cellstranslationinitiationcorrectedfactoreif4ai AT tamakiishima anoveltargetofactionofminocyclineinngfinducedneuriteoutgrowthinpc12cellstranslationinitiationcorrectedfactoreif4ai AT kenjihashimoto noveltargetofactionofminocyclineinngfinducedneuriteoutgrowthinpc12cellstranslationinitiationcorrectedfactoreif4ai AT tamakiishima noveltargetofactionofminocyclineinngfinducedneuriteoutgrowthinpc12cellstranslationinitiationcorrectedfactoreif4ai
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A novel target of action of minocycline in NGF-induced neurite outgrowth in PC12 cells: translation initiation [corrected] factor eIF4AI.

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