Novel squamosamide derivative (compound FLZ) attenuates Abeta25-35-induced toxicity in SH-SY5Y cells.
OBJECTIVE
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.


CONCLUSIONS
FLZ has protective action against Abeta25-35-induced toxicity in SH-SY5Y cells, which might be mediated through its antioxidant property.
Fang
Fang
F
Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
Liu
Geng-tao
GT
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D044482:Benzeneacetamides / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010636:Phenols / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D016229:Amyloid beta-Peptides; D044482:Benzeneacetamides; D010446:Peptide Fragments; D010636:Phenols; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); C084439:squamosamide; D007770:L-Lactate Dehydrogenase; D005978:Glutathione