Abstract
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 Aβ25–35-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 Aβ25–35 (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 Aβ25–35-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 Aβ25–35 in SH-SY5Y cells.
Conclusion:
FLZ has protective action against Aβ25–35-in-duced toxicity in SH-SY5Y cells, which might be mediated through its antioxidant property.
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Project supported by the Ministry of Science and Technology of China (No 2007CB507400).
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Fang, F., Liu, Gt. Novel squamosamide derivative (compound FLZ) attenuates Aβ25–35-induced toxicity in SH-SY5Y cells. Acta Pharmacol Sin 29, 152–160 (2008). https://doi.org/10.1111/j.1745-7254.2008.00714.x
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DOI: https://doi.org/10.1111/j.1745-7254.2008.00714.x
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