Differential effect of PMS777, a new type of acetylcholinesterase inhibitor, and galanthamine on oxidative injury induced in human neuroblastoma SK-N-SH cells
| Autor: | Miezan J.-M. Ezoulin, Juan Li, Guirong Wu, Chang-Zhi Dong, Jean-Edouard Ombetta, Hong-Zhuan Chen, France Massicot, Françoise Heymans |
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| Rok vydání: | 2005 |
| Předmět: |
Lipopolysaccharides
Cell Survival medicine.drug_class Mitochondrion Pharmacology medicine.disease_cause Neuroblastoma chemistry.chemical_compound Alzheimer Disease Cell Line Tumor medicine Humans Platelet Activating Factor Furans Butyrylcholinesterase Cholinesterase Neurons Platelet-activating factor biology Galantamine General Neuroscience Glutathione Acetylcholinesterase Mitochondria Oxidative Stress Neuroprotective Agents chemistry Acetylcholinesterase inhibitor Biochemistry biology.protein Encephalitis Cholinesterase Inhibitors Inflammation Mediators Reactive Oxygen Species Oxidative stress Interleukin-1 |
| Zdroj: | Neuroscience Letters. 389:61-65 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2005.07.026 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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