Differential effect of PMS777, a new type of acetylcholinesterase inhibitor, and galanthamine on oxidative injury induced in human neuroblastoma SK-N-SH cells.
Neurosci Lett
; 389(2): 61-5, 2005 Dec 02.
Article
en En
| MEDLINE
| ID: mdl-16095823
In the search for highly selective and potent cholinesterase inhibitors (AChEI) being able to improve oxidative injury, PMS777, a tetrahydrofuran derivative, was designed as a novel dual PAF and acetylcholinesterase inhibitor. The aim of this study was to investigate the modulatory effects of PMS777 and galanthamine, another AChEI, on the oxidative injury induced in neuronal cells. The SK-N-SH cells stimulated with LPS+IL-(1beta) were selected to investigate the direct inhibitory effect of PMS777 and galanthamine. LPS+IL-(1beta) induced oxidative injury as assessed by ROS production (29%), GSH depletion (11%) and loss of mitochondrial activity (22%). GSH depletion was never decreased by either drug. In contrast, ROS production and mitochondrial activity were totally prevented by addition of PMS777 but not galanthamine. PMS777 also inhibits butylcholinesterase and it shows selectivity for acetylcholinesterase. Thus, this PAF antagonist inaugurates a new type of AChEI, able to fight oxidative injury. Therefore, PMS777 could be of interest on patients with cognitive impairments and inflammatory damage, as in AD.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor de Activación Plaquetaria
/
Inhibidores de la Colinesterasa
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Estrés Oxidativo
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Mediadores de Inflamación
/
Furanos
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Galantamina
/
Neuronas
Límite:
Humans
Idioma:
En
Revista:
Neurosci Lett
Año:
2005
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Irlanda