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

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 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
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 29 Issue 2 Pg. 152-60 (Feb 2008) ISSN: 1671-4083 [Print] United States
• PMID: 18215343 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Benzeneacetamides
• Peptide Fragments
• Phenols
• Reactive Oxygen Species
• amyloid beta-protein (25-35)
• squamosamide
• L-Lactate Dehydrogenase
• Glutathione

Topics

• Amyloid beta-Peptides (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)