Undifferentiated and differentiated PC12 cells protected by huprines against injury induced by hydrogen peroxide

Autor: Pera, Marta, Camps García, Pelayo, Muñoz-Torrero López-Ibarra, Diego, Pérez Fernández, Belén, Badía, A. (Albert), Clos, Victòria
Přispěvatelé: Universitat de Barcelona
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Recercat. Dipósit de la Recerca de Catalunya
instname
Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona
Dipòsit Digital de la UB
Universidad de Barcelona
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: