Open AccessNovel squamosamide derivative (compound FLZ) attenuates Aβ 25–35 ‐induced toxicity in SH‐SY5Y cells 1
Author(s) -
FANG Fang,
LIU Gengtao
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00714.x
Subject(s) - sh sy5y , glutathione , apoptosis , lactate dehydrogenase , viability assay , reactive oxygen species , toxicity , intracellular , chemistry , cytochrome c , biochemistry , pharmacology , biology , cell culture , enzyme , neuroblastoma , genetics , organic chemistry
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 Aβ 25–35 ‐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 Aβ 25–35 (25 μmol/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 μmol/L) markedly increased cell viability and decreased LDH release and morphological injury. Also, FLZ attenuated the Aβ 25–35 ‐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 Aβ 25–35 in SH‐SY5Y cells. Conclusion: FLZ has protective action against Aβ 25–35 ‐in‐duced toxicity in SH‐SY5Y cells, which might be mediated through its antioxidant property.