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Aberrant Neuronal Differentiation and Inhibition of Dendrite Outgrowth Resulting from Endoplasmic Reticulum Stress

Neural stem cells (NSCs) play an essential role in development of the central nervous system. Endoplasmic reticulum (ER) stress induces neuronal death. After neuronal death, neurogenesis is generally enhanced to repair the damaged regions. However, it is unclear whether ER stress directly affects ne...

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Autores principales: Kawada, Koichi, Iekumo, Takaaki, Saito, Ryo, Kaneko, Masayuki, Mimori, Seisuke, Nomura, Yasuyuki, Okuma, Yasunobu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320781/
https://www.ncbi.nlm.nih.gov/pubmed/24723324
http://dx.doi.org/10.1002/jnr.23389
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author Kawada, Koichi
Iekumo, Takaaki
Saito, Ryo
Kaneko, Masayuki
Mimori, Seisuke
Nomura, Yasuyuki
Okuma, Yasunobu
author_facet Kawada, Koichi
Iekumo, Takaaki
Saito, Ryo
Kaneko, Masayuki
Mimori, Seisuke
Nomura, Yasuyuki
Okuma, Yasunobu
author_sort Kawada, Koichi
collection PubMed
description Neural stem cells (NSCs) play an essential role in development of the central nervous system. Endoplasmic reticulum (ER) stress induces neuronal death. After neuronal death, neurogenesis is generally enhanced to repair the damaged regions. However, it is unclear whether ER stress directly affects neurogenesis-related processes such as neuronal differentiation and dendrite outgrowth. We evaluated whether neuronal differentiation and dendrite outgrowth were regulated by HRD1, a ubiquitin ligase that was induced under mild conditions of tunicamycin-induced ER stress. Neurons were differentiated from mouse embryonic carcinoma P19 cells by using retinoic acid. The differentiated cells were cultured for 8 days with or without tunicamycin and HRD1 knockdown. The ER stressor led to markedly increased levels of ER stress. ER stress increased the expression levels of neuronal marker βIII-tubulin in 8-day-differentiated cells. However, the neurites of dendrite marker microtubule-associated protein-2 (MAP-2)-positive cells appeared to retract in response to ER stress. Moreover, ER stress markedly reduced the dendrite length and MAP-2 expression levels, whereas it did not affect the number of surviving mature neurons. In contrast, HRD1 knockdown abolished the changes in expression of proteins such as βIII-tubulin and MAP-2. These results suggested that ER stress caused aberrant neuronal differentiation from NSCs followed by the inhibition of neurite outgrowth. These events may be mediated by increased HRD1 expression.
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spelling pubmed-43207812015-02-13 Aberrant Neuronal Differentiation and Inhibition of Dendrite Outgrowth Resulting from Endoplasmic Reticulum Stress Kawada, Koichi Iekumo, Takaaki Saito, Ryo Kaneko, Masayuki Mimori, Seisuke Nomura, Yasuyuki Okuma, Yasunobu J Neurosci Res Research Articles Neural stem cells (NSCs) play an essential role in development of the central nervous system. Endoplasmic reticulum (ER) stress induces neuronal death. After neuronal death, neurogenesis is generally enhanced to repair the damaged regions. However, it is unclear whether ER stress directly affects neurogenesis-related processes such as neuronal differentiation and dendrite outgrowth. We evaluated whether neuronal differentiation and dendrite outgrowth were regulated by HRD1, a ubiquitin ligase that was induced under mild conditions of tunicamycin-induced ER stress. Neurons were differentiated from mouse embryonic carcinoma P19 cells by using retinoic acid. The differentiated cells were cultured for 8 days with or without tunicamycin and HRD1 knockdown. The ER stressor led to markedly increased levels of ER stress. ER stress increased the expression levels of neuronal marker βIII-tubulin in 8-day-differentiated cells. However, the neurites of dendrite marker microtubule-associated protein-2 (MAP-2)-positive cells appeared to retract in response to ER stress. Moreover, ER stress markedly reduced the dendrite length and MAP-2 expression levels, whereas it did not affect the number of surviving mature neurons. In contrast, HRD1 knockdown abolished the changes in expression of proteins such as βIII-tubulin and MAP-2. These results suggested that ER stress caused aberrant neuronal differentiation from NSCs followed by the inhibition of neurite outgrowth. These events may be mediated by increased HRD1 expression. BlackWell Publishing Ltd 2014-09 2014-04-10 /pmc/articles/PMC4320781/ /pubmed/24723324 http://dx.doi.org/10.1002/jnr.23389 Text en © 2014 The Authors Journal of Neuroscience Research Published by Wiley Periodicals, Inc. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Kawada, Koichi
Iekumo, Takaaki
Saito, Ryo
Kaneko, Masayuki
Mimori, Seisuke
Nomura, Yasuyuki
Okuma, Yasunobu
Aberrant Neuronal Differentiation and Inhibition of Dendrite Outgrowth Resulting from Endoplasmic Reticulum Stress
title Aberrant Neuronal Differentiation and Inhibition of Dendrite Outgrowth Resulting from Endoplasmic Reticulum Stress
title_full Aberrant Neuronal Differentiation and Inhibition of Dendrite Outgrowth Resulting from Endoplasmic Reticulum Stress
title_fullStr Aberrant Neuronal Differentiation and Inhibition of Dendrite Outgrowth Resulting from Endoplasmic Reticulum Stress
title_full_unstemmed Aberrant Neuronal Differentiation and Inhibition of Dendrite Outgrowth Resulting from Endoplasmic Reticulum Stress
title_short Aberrant Neuronal Differentiation and Inhibition of Dendrite Outgrowth Resulting from Endoplasmic Reticulum Stress
title_sort aberrant neuronal differentiation and inhibition of dendrite outgrowth resulting from endoplasmic reticulum stress
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320781/
https://www.ncbi.nlm.nih.gov/pubmed/24723324
http://dx.doi.org/10.1002/jnr.23389
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