Undifferentiated and differentiated PC12 cells protected by huprines against injury induced by hydrogen peroxide.
Oxidative stress is implicated in the pathogenesis of neurodegenerative disorders and hydrogen peroxide (H2O2) plays a central role in the stress. Huprines, a group of potent acetylcholinesterase inhibitors (AChEIs), have shown a broad cholinergic pharmacological profile. Recently, it has been obser...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3781080?pdf=render |
| _version_ | 1818107703238590464 |
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| author | Marta Pera Pelayo Camps Diego Muñoz-Torrero Belen Perez Albert Badia M Victoria Clos Guillen |
| author_facet | Marta Pera Pelayo Camps Diego Muñoz-Torrero Belen Perez Albert Badia M Victoria Clos Guillen |
| author_sort | Marta Pera |
| collection | DOAJ |
| description | Oxidative stress is implicated in the pathogenesis of neurodegenerative disorders and hydrogen peroxide (H2O2) plays a central role in the stress. Huprines, a group of potent acetylcholinesterase inhibitors (AChEIs), have shown a broad cholinergic pharmacological profile. Recently, it has been observed that huprine X (HX) improves cognition in non transgenic middle aged mice and shows a neuroprotective activity (increased synaptophysin expression) in 3xTg-AD mice. Consequently, in the present experiments the potential neuroprotective effect of huprines (HX, HY, HZ) has been analyzed in two different in vitro conditions: undifferentiated and NGF-differentiated PC12 cells. Cells were subjected to oxidative insult (H2O2, 200 µM) and the protective effects of HX, HY and HZ (0.01 µM-1 µM) were analyzed after a pre-incubation period of 24 and 48 hours. All huprines showed protective effects in both undifferentiated and NGF-differentiated cells, however only in differentiated cells the effect was dependent on cholinergic receptors as atropine (muscarinic antagonist, 0.1 µM) and mecamylamine (nicotinic antagonist, 100 µM) reverted the neuroprotection action of huprines. The decrease in SOD activity observed after oxidative insult was overcome in the presence of huprines and this effect was not mediated by muscarinic or nicotinic receptors. In conclusion, huprines displayed neuroprotective properties as previously observed in in vivo studies. In addition, these effects were mediated by cholinergic receptors only in differentiated cells. However, a non-cholinergic mechanism, probably through an increase in SOD activity, seems to be also involved in the neuroprotective effects of huprines. |
| first_indexed | 2024-12-11T02:03:41Z |
| format | Article |
| id | doaj.art-fd57570af2554985b3e385ddb2ac9cf3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T02:03:41Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fd57570af2554985b3e385ddb2ac9cf32022-12-22T01:24:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7434410.1371/journal.pone.0074344Undifferentiated and differentiated PC12 cells protected by huprines against injury induced by hydrogen peroxide.Marta PeraPelayo CampsDiego Muñoz-TorreroBelen PerezAlbert BadiaM Victoria Clos GuillenOxidative stress is implicated in the pathogenesis of neurodegenerative disorders and hydrogen peroxide (H2O2) plays a central role in the stress. Huprines, a group of potent acetylcholinesterase inhibitors (AChEIs), have shown a broad cholinergic pharmacological profile. Recently, it has been observed that huprine X (HX) improves cognition in non transgenic middle aged mice and shows a neuroprotective activity (increased synaptophysin expression) in 3xTg-AD mice. Consequently, in the present experiments the potential neuroprotective effect of huprines (HX, HY, HZ) has been analyzed in two different in vitro conditions: undifferentiated and NGF-differentiated PC12 cells. Cells were subjected to oxidative insult (H2O2, 200 µM) and the protective effects of HX, HY and HZ (0.01 µM-1 µM) were analyzed after a pre-incubation period of 24 and 48 hours. All huprines showed protective effects in both undifferentiated and NGF-differentiated cells, however only in differentiated cells the effect was dependent on cholinergic receptors as atropine (muscarinic antagonist, 0.1 µM) and mecamylamine (nicotinic antagonist, 100 µM) reverted the neuroprotection action of huprines. The decrease in SOD activity observed after oxidative insult was overcome in the presence of huprines and this effect was not mediated by muscarinic or nicotinic receptors. In conclusion, huprines displayed neuroprotective properties as previously observed in in vivo studies. In addition, these effects were mediated by cholinergic receptors only in differentiated cells. However, a non-cholinergic mechanism, probably through an increase in SOD activity, seems to be also involved in the neuroprotective effects of huprines.http://europepmc.org/articles/PMC3781080?pdf=render |
| spellingShingle | Marta Pera Pelayo Camps Diego Muñoz-Torrero Belen Perez Albert Badia M Victoria Clos Guillen Undifferentiated and differentiated PC12 cells protected by huprines against injury induced by hydrogen peroxide. PLoS ONE |
| title | Undifferentiated and differentiated PC12 cells protected by huprines against injury induced by hydrogen peroxide. |
| title_full | Undifferentiated and differentiated PC12 cells protected by huprines against injury induced by hydrogen peroxide. |
| title_fullStr | Undifferentiated and differentiated PC12 cells protected by huprines against injury induced by hydrogen peroxide. |
| title_full_unstemmed | Undifferentiated and differentiated PC12 cells protected by huprines against injury induced by hydrogen peroxide. |
| title_short | Undifferentiated and differentiated PC12 cells protected by huprines against injury induced by hydrogen peroxide. |
| title_sort | undifferentiated and differentiated pc12 cells protected by huprines against injury induced by hydrogen peroxide |
| url | http://europepmc.org/articles/PMC3781080?pdf=render |
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