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Pomalidomide Ameliorates H(2)O(2)-Induced Oxidative Stress Injury and Cell Death in Rat Primary Cortical Neuronal Cultures by Inducing Anti-Oxidative and Anti-Apoptosis Effects

Due to its high oxygen demand and abundance of peroxidation-susceptible lipid cells, the brain is particularly vulnerable to oxidative stress. Induced by a redox state imbalance involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system, oxidative...

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Autores principales: Tsai, Yan-Rou, Chang, Cheng-Fu, Lai, Jing-Huei, Wu, John Chung-Che, Chen, Yen-Hua, Kang, Shuo-Jhen, Hoffer, Barry J., Tweedie, David, Luo, Weiming, Greig, Nigel H., Chiang, Yung-Hsiao, Chen, Kai-Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213994/
https://www.ncbi.nlm.nih.gov/pubmed/30347766
http://dx.doi.org/10.3390/ijms19103252
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author Tsai, Yan-Rou
Chang, Cheng-Fu
Lai, Jing-Huei
Wu, John Chung-Che
Chen, Yen-Hua
Kang, Shuo-Jhen
Hoffer, Barry J.
Tweedie, David
Luo, Weiming
Greig, Nigel H.
Chiang, Yung-Hsiao
Chen, Kai-Yun
author_facet Tsai, Yan-Rou
Chang, Cheng-Fu
Lai, Jing-Huei
Wu, John Chung-Che
Chen, Yen-Hua
Kang, Shuo-Jhen
Hoffer, Barry J.
Tweedie, David
Luo, Weiming
Greig, Nigel H.
Chiang, Yung-Hsiao
Chen, Kai-Yun
author_sort Tsai, Yan-Rou
collection PubMed
description Due to its high oxygen demand and abundance of peroxidation-susceptible lipid cells, the brain is particularly vulnerable to oxidative stress. Induced by a redox state imbalance involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system, oxidative stress plays a central role in a common pathophysiology that underpins neuronal cell death in acute neurological disorders epitomized by stroke and chronic ones such as Alzheimer’s disease. After cerebral ischemia, for example, inflammation bears a key responsibility in the development of permanent neurological damage. ROS are involved in the mechanism of post-ischemic inflammation. The activation of several inflammatory enzymes produces ROS, which subsequently suppress mitochondrial activity, leading to further tissue damage. Pomalidomide (POM) is a clinically available immunomodulatory and anti-inflammatory agent. Using H(2)O(2)-treated rat primary cortical neuronal cultures, we found POM displayed neuroprotective effects against oxidative stress and cell death that associated with changes in the nuclear factor erythroid derived 2/superoxide dismutase 2/catalase signaling pathway. POM also suppressed nuclear factor kappa-light-chain-enhancer (NF-κB) levels and significantly mitigated cortical neuronal apoptosis by regulating Bax, Cytochrome c and Poly (ADP-ribose) polymerase. In summary, POM exerted neuroprotective effects via its anti-oxidative and anti-inflammatory actions against H(2)O(2)-induced injury. POM consequently represents a potential therapeutic agent against brain damage and related disorders and warrants further evaluation.
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spelling pubmed-62139942018-11-14 Pomalidomide Ameliorates H(2)O(2)-Induced Oxidative Stress Injury and Cell Death in Rat Primary Cortical Neuronal Cultures by Inducing Anti-Oxidative and Anti-Apoptosis Effects Tsai, Yan-Rou Chang, Cheng-Fu Lai, Jing-Huei Wu, John Chung-Che Chen, Yen-Hua Kang, Shuo-Jhen Hoffer, Barry J. Tweedie, David Luo, Weiming Greig, Nigel H. Chiang, Yung-Hsiao Chen, Kai-Yun Int J Mol Sci Article Due to its high oxygen demand and abundance of peroxidation-susceptible lipid cells, the brain is particularly vulnerable to oxidative stress. Induced by a redox state imbalance involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system, oxidative stress plays a central role in a common pathophysiology that underpins neuronal cell death in acute neurological disorders epitomized by stroke and chronic ones such as Alzheimer’s disease. After cerebral ischemia, for example, inflammation bears a key responsibility in the development of permanent neurological damage. ROS are involved in the mechanism of post-ischemic inflammation. The activation of several inflammatory enzymes produces ROS, which subsequently suppress mitochondrial activity, leading to further tissue damage. Pomalidomide (POM) is a clinically available immunomodulatory and anti-inflammatory agent. Using H(2)O(2)-treated rat primary cortical neuronal cultures, we found POM displayed neuroprotective effects against oxidative stress and cell death that associated with changes in the nuclear factor erythroid derived 2/superoxide dismutase 2/catalase signaling pathway. POM also suppressed nuclear factor kappa-light-chain-enhancer (NF-κB) levels and significantly mitigated cortical neuronal apoptosis by regulating Bax, Cytochrome c and Poly (ADP-ribose) polymerase. In summary, POM exerted neuroprotective effects via its anti-oxidative and anti-inflammatory actions against H(2)O(2)-induced injury. POM consequently represents a potential therapeutic agent against brain damage and related disorders and warrants further evaluation. MDPI 2018-10-19 /pmc/articles/PMC6213994/ /pubmed/30347766 http://dx.doi.org/10.3390/ijms19103252 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tsai, Yan-Rou
Chang, Cheng-Fu
Lai, Jing-Huei
Wu, John Chung-Che
Chen, Yen-Hua
Kang, Shuo-Jhen
Hoffer, Barry J.
Tweedie, David
Luo, Weiming
Greig, Nigel H.
Chiang, Yung-Hsiao
Chen, Kai-Yun
Pomalidomide Ameliorates H(2)O(2)-Induced Oxidative Stress Injury and Cell Death in Rat Primary Cortical Neuronal Cultures by Inducing Anti-Oxidative and Anti-Apoptosis Effects
title Pomalidomide Ameliorates H(2)O(2)-Induced Oxidative Stress Injury and Cell Death in Rat Primary Cortical Neuronal Cultures by Inducing Anti-Oxidative and Anti-Apoptosis Effects
title_full Pomalidomide Ameliorates H(2)O(2)-Induced Oxidative Stress Injury and Cell Death in Rat Primary Cortical Neuronal Cultures by Inducing Anti-Oxidative and Anti-Apoptosis Effects
title_fullStr Pomalidomide Ameliorates H(2)O(2)-Induced Oxidative Stress Injury and Cell Death in Rat Primary Cortical Neuronal Cultures by Inducing Anti-Oxidative and Anti-Apoptosis Effects
title_full_unstemmed Pomalidomide Ameliorates H(2)O(2)-Induced Oxidative Stress Injury and Cell Death in Rat Primary Cortical Neuronal Cultures by Inducing Anti-Oxidative and Anti-Apoptosis Effects
title_short Pomalidomide Ameliorates H(2)O(2)-Induced Oxidative Stress Injury and Cell Death in Rat Primary Cortical Neuronal Cultures by Inducing Anti-Oxidative and Anti-Apoptosis Effects
title_sort pomalidomide ameliorates h(2)o(2)-induced oxidative stress injury and cell death in rat primary cortical neuronal cultures by inducing anti-oxidative and anti-apoptosis effects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213994/
https://www.ncbi.nlm.nih.gov/pubmed/30347766
http://dx.doi.org/10.3390/ijms19103252
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