N-acetylcysteine protects against apoptosis through modulation of group I metabotropic glutamate receptor activity.

The activation of group I metabotropic glutamate receptor (group I mGlus) has been shown to produce neuroprotective or neurotoxic effects. In this study, we investigated the effects of N-acetylcysteine (NAC), a precursor of the antioxidant glutathione, on group I mGlus activation in apoptosis of gli...

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Main Authors: Lili Sun, Li Gu, Shuting Wang, Jifang Yuan, Huimin Yang, Jiawei Zhu, Hong Zhang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3307713?pdf=render
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spelling doaj-86fa617a45824aeb92bd15b35c8b3a282020-11-25T01:47:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3250310.1371/journal.pone.0032503N-acetylcysteine protects against apoptosis through modulation of group I metabotropic glutamate receptor activity.Lili SunLi GuShuting WangJifang YuanHuimin YangJiawei ZhuHong ZhangThe activation of group I metabotropic glutamate receptor (group I mGlus) has been shown to produce neuroprotective or neurotoxic effects. In this study, we investigated the effects of N-acetylcysteine (NAC), a precursor of the antioxidant glutathione, on group I mGlus activation in apoptosis of glial C6 and MN9D cell lines, and a rat model of Parkinson's disease (PD). We demonstrated that NAC protected against apoptosis through modulation of group I mGlus activity. In glial C6 cells, NAC promoted phosphorylation of ERK induced by (s)-3,5-dihydroxy-phenylglycine (DHPG), an agonist of group I mGlus. NAC enhanced the group I mGlus-mediated protection from staurosporine (STS)-induced apoptosis following DHPG treatment. Moreover, in rotenone-treated MN9D cells and PD rat model, NAC protected against group I mGlus-induced toxicity by compromising the decrease in phosphorylation of ERK, phosphorylation or expression level of TH. Furthermore, the results showed that NAC prohibited the level of ROS and oxidation of cellular GSH/GSSG (E(h)) accompanied by activated group I mGlus in the experimental models. Our results suggest that NAC might act as a regulator of group I mGlus-mediated activities in both neuroprotection and neurotoxicity via reducing the oxidative stress, eventually to protect cell survival. The study also suggests that NAC might be a potential therapeutics targeting for group I mGlus activation in the treatment of PD.http://europepmc.org/articles/PMC3307713?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Lili Sun
Li Gu
Shuting Wang
Jifang Yuan
Huimin Yang
Jiawei Zhu
Hong Zhang
spellingShingle Lili Sun
Li Gu
Shuting Wang
Jifang Yuan
Huimin Yang
Jiawei Zhu
Hong Zhang
N-acetylcysteine protects against apoptosis through modulation of group I metabotropic glutamate receptor activity.
PLoS ONE
author_facet Lili Sun
Li Gu
Shuting Wang
Jifang Yuan
Huimin Yang
Jiawei Zhu
Hong Zhang
author_sort Lili Sun
title N-acetylcysteine protects against apoptosis through modulation of group I metabotropic glutamate receptor activity.
title_short N-acetylcysteine protects against apoptosis through modulation of group I metabotropic glutamate receptor activity.
title_full N-acetylcysteine protects against apoptosis through modulation of group I metabotropic glutamate receptor activity.
title_fullStr N-acetylcysteine protects against apoptosis through modulation of group I metabotropic glutamate receptor activity.
title_full_unstemmed N-acetylcysteine protects against apoptosis through modulation of group I metabotropic glutamate receptor activity.
title_sort n-acetylcysteine protects against apoptosis through modulation of group i metabotropic glutamate receptor activity.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2012-01-01
description The activation of group I metabotropic glutamate receptor (group I mGlus) has been shown to produce neuroprotective or neurotoxic effects. In this study, we investigated the effects of N-acetylcysteine (NAC), a precursor of the antioxidant glutathione, on group I mGlus activation in apoptosis of glial C6 and MN9D cell lines, and a rat model of Parkinson's disease (PD). We demonstrated that NAC protected against apoptosis through modulation of group I mGlus activity. In glial C6 cells, NAC promoted phosphorylation of ERK induced by (s)-3,5-dihydroxy-phenylglycine (DHPG), an agonist of group I mGlus. NAC enhanced the group I mGlus-mediated protection from staurosporine (STS)-induced apoptosis following DHPG treatment. Moreover, in rotenone-treated MN9D cells and PD rat model, NAC protected against group I mGlus-induced toxicity by compromising the decrease in phosphorylation of ERK, phosphorylation or expression level of TH. Furthermore, the results showed that NAC prohibited the level of ROS and oxidation of cellular GSH/GSSG (E(h)) accompanied by activated group I mGlus in the experimental models. Our results suggest that NAC might act as a regulator of group I mGlus-mediated activities in both neuroprotection and neurotoxicity via reducing the oxidative stress, eventually to protect cell survival. The study also suggests that NAC might be a potential therapeutics targeting for group I mGlus activation in the treatment of PD.
url http://europepmc.org/articles/PMC3307713?pdf=render
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