Undifferentiated and differentiated PC12 cells protected by huprines against injury induced by hydrogen peroxide
Pera Muñoz, Marta (Universitat Autònoma de Barcelona. Institut de Neurociències)
Camps García, Pelayo (Universitat de Barcelona. Laboratori de Química Farmacèutica)
Muñoz-Torrero López-Ibarra, Diego (Universitat de Barcelona. Laboratori de Química Farmacèutica)
Pérez, Belén (Universitat Autònoma de Barcelona. Institut de Neurociències)
Badía, A. (Albert) (Universitat Autònoma de Barcelona. Institut de Neurociències)
Clos, Victòria (Universitat Autònoma de Barcelona. Institut de Neurociències)

Data:	2013
Resum:	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 noncholinergic mechanism, probably through an increase in SOD activity, seems to be also involved in the neuroprotective effects of huprines.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Acetilcolinesterasa ; Inhibidors ; Estrès oxidatiu ; Peròxids
Publicat a:	PloS one, Vol. 8 Núm. 9 (September 2013) , p. e74344, ISSN 1932-6203

DOI: 10.1371/journal.pone.0074344
PMID: 24086337

8 p, 592.8 KB

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