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Plasmalogens Rescue Neuronal Cell Death through an Activation of AKT and ERK Survival Signaling

Neuronal cells are susceptible to many stresses, which will cause the apoptosis and neurodegenerative diseases. The precise molecular mechanism behind the neuronal protection against these apoptotic stimuli is necessary for drug discovery. In the present study, we have found that plasmalogens (Pls),...

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Autores principales: Hossain, Md. Shamim, Ifuku, Masataka, Take, Sachiko, Kawamura, Jun, Miake, Kiyotaka, Katafuchi, Toshihiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869814/
https://www.ncbi.nlm.nih.gov/pubmed/24376709
http://dx.doi.org/10.1371/journal.pone.0083508
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author Hossain, Md. Shamim
Ifuku, Masataka
Take, Sachiko
Kawamura, Jun
Miake, Kiyotaka
Katafuchi, Toshihiko
author_facet Hossain, Md. Shamim
Ifuku, Masataka
Take, Sachiko
Kawamura, Jun
Miake, Kiyotaka
Katafuchi, Toshihiko
author_sort Hossain, Md. Shamim
collection PubMed
description Neuronal cells are susceptible to many stresses, which will cause the apoptosis and neurodegenerative diseases. The precise molecular mechanism behind the neuronal protection against these apoptotic stimuli is necessary for drug discovery. In the present study, we have found that plasmalogens (Pls), which are glycerophospholipids containing vinyl ether linkage at sn-1 position, can protect the neuronal cell death upon serum deprivation. Interestingly, caspse-9, but not caspase-8 and caspase-12, was cleaved upon the serum starvation in Neuro-2A cells. Pls treatments effectively reduced the activation of caspase-9. Furthermore, cellular signaling experiments showed that Pls enhanced phosphorylation of the phosphoinositide 3-kinase (PI3K)-dependent serine/threonine-specific protein kinase AKT and extracellular-signal-regulated kinases ERK1/2. PI3K/AKT inhibitor LY294002 and MAPK/ERK kinase (MEK) inhibitor U0126 treatments study clearly indicated that Pls-mediated cell survival was dependent on the activation of these kinases. In addition, Pls also inhibited primary mouse hippocampal neuronal cell death induced by nutrient deprivation, which was associated with the inhibition of caspase-9 and caspase-3 cleavages. It was reported that Pls content decreased in the brain of the Alzheimer’s patients, which indicated that the reduction of Pls content could endanger neurons. The present findings, taken together, suggest that Pls have an anti-apoptotic action in the brain. Further studies on precise mechanisms of Pls-mediated protection against cell death may lead us to establish a novel therapeutic approach to cure neurodegenerative disorders.
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spelling pubmed-38698142013-12-27 Plasmalogens Rescue Neuronal Cell Death through an Activation of AKT and ERK Survival Signaling Hossain, Md. Shamim Ifuku, Masataka Take, Sachiko Kawamura, Jun Miake, Kiyotaka Katafuchi, Toshihiko PLoS One Research Article Neuronal cells are susceptible to many stresses, which will cause the apoptosis and neurodegenerative diseases. The precise molecular mechanism behind the neuronal protection against these apoptotic stimuli is necessary for drug discovery. In the present study, we have found that plasmalogens (Pls), which are glycerophospholipids containing vinyl ether linkage at sn-1 position, can protect the neuronal cell death upon serum deprivation. Interestingly, caspse-9, but not caspase-8 and caspase-12, was cleaved upon the serum starvation in Neuro-2A cells. Pls treatments effectively reduced the activation of caspase-9. Furthermore, cellular signaling experiments showed that Pls enhanced phosphorylation of the phosphoinositide 3-kinase (PI3K)-dependent serine/threonine-specific protein kinase AKT and extracellular-signal-regulated kinases ERK1/2. PI3K/AKT inhibitor LY294002 and MAPK/ERK kinase (MEK) inhibitor U0126 treatments study clearly indicated that Pls-mediated cell survival was dependent on the activation of these kinases. In addition, Pls also inhibited primary mouse hippocampal neuronal cell death induced by nutrient deprivation, which was associated with the inhibition of caspase-9 and caspase-3 cleavages. It was reported that Pls content decreased in the brain of the Alzheimer’s patients, which indicated that the reduction of Pls content could endanger neurons. The present findings, taken together, suggest that Pls have an anti-apoptotic action in the brain. Further studies on precise mechanisms of Pls-mediated protection against cell death may lead us to establish a novel therapeutic approach to cure neurodegenerative disorders. Public Library of Science 2013-12-20 /pmc/articles/PMC3869814/ /pubmed/24376709 http://dx.doi.org/10.1371/journal.pone.0083508 Text en © 2013 Hossain 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
Hossain, Md. Shamim
Ifuku, Masataka
Take, Sachiko
Kawamura, Jun
Miake, Kiyotaka
Katafuchi, Toshihiko
Plasmalogens Rescue Neuronal Cell Death through an Activation of AKT and ERK Survival Signaling
title Plasmalogens Rescue Neuronal Cell Death through an Activation of AKT and ERK Survival Signaling
title_full Plasmalogens Rescue Neuronal Cell Death through an Activation of AKT and ERK Survival Signaling
title_fullStr Plasmalogens Rescue Neuronal Cell Death through an Activation of AKT and ERK Survival Signaling
title_full_unstemmed Plasmalogens Rescue Neuronal Cell Death through an Activation of AKT and ERK Survival Signaling
title_short Plasmalogens Rescue Neuronal Cell Death through an Activation of AKT and ERK Survival Signaling
title_sort plasmalogens rescue neuronal cell death through an activation of akt and erk survival signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869814/
https://www.ncbi.nlm.nih.gov/pubmed/24376709
http://dx.doi.org/10.1371/journal.pone.0083508
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