Document Detail


Novel squamosamide derivative (compound FLZ) attenuates Abeta25-35-induced toxicity in SH-SY5Y cells.
MedLine Citation:
PMID:  18215343     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: The aim of the present study was to investigate the protective effect of compound N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide (compound FLZ), a novel synthetic analogue of nature squamosamide, on Abeta25-35-induced toxicity and its active mechanism in human neuroblastoma SH-SY5Y cells. METHODS: SH-SY5Y cells were pre-incubated with various concentrations of compound FLZ for 30 min and then cultivated with Abeta25-35 (25 micromol/L) for 48 h to induce neurotoxicity. Cell viability, lactate dehydrogenase (LDH) release, and the glutathione (GSH) level were determined by a biochemical analysis. The cell apoptotic ratio and intracellular reactive oxygen species (ROS) level were measured by a flow cytometry analysis. The expression of apoptosis protein (Bcl-2 and Bax) and cytochrome c release were assayed by the Western blot method. RESULTS: The pretreatment of SH-SY5Y cells with FLZ (1 and 10 micromol/L) markedly increased cell viability and decreased LDH release and morphological injury. Also, FLZ attenuated the Abeta25-35-induced apoptotic cell ratio, regulated the apoptosis protein (Bcl-2 and Bax) expression, and decreased the cytochrome c release from mitochondria. FLZ also significantly inhibited the generation of ROS and the depletion of GSH induced by Abeta25-35 in SH-SY5Y cells. CONCLUSION: FLZ has protective action against Abeta25-35-induced toxicity in SH-SY5Y cells, which might be mediated through its antioxidant property.
Authors:
Fang Fang; Geng-tao Liu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Acta pharmacologica Sinica     Volume:  29     ISSN:  1671-4083     ISO Abbreviation:  Acta Pharmacol. Sin.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-24     Completed Date:  2009-05-04     Revised Date:  2010-06-07    
Medline Journal Info:
Nlm Unique ID:  100956087     Medline TA:  Acta Pharmacol Sin     Country:  China    
Other Details:
Languages:  eng     Pagination:  152-60     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
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MeSH Terms
Descriptor/Qualifier:
Amyloid beta-Protein / antagonists & inhibitors*,  toxicity*
Apoptosis / drug effects
Benzeneacetamides / pharmacology*
Cell Line
Cell Survival
Glutathione / metabolism
Humans
L-Lactate Dehydrogenase / metabolism
Peptide Fragments / antagonists & inhibitors*,  toxicity*
Phenols / pharmacology*
Reactive Oxygen Species / metabolism
Chemical
Reg. No./Substance:
0/Amyloid beta-Protein; 0/Benzeneacetamides; 0/Peptide Fragments; 0/Phenols; 0/Reactive Oxygen Species; 0/amyloid beta-protein (25-35); 142750-35-4/squamosamide; 70-18-8/Glutathione; EC 1.1.1.27/L-Lactate Dehydrogenase

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