Protective effects of compound FLZ, a novel synthetic analogue of squamosamide, on Β-amyloid-induced rat brain mitochondrial dysfunction in vitro

Abstract

Aim: The aim of the present study was to assess the effects of N-[2-(4-hydroxyphenyl)ethyl]-2-(2,5-dimethoxyphenyl)-3-(3-methoxy-4- hydroxyphenyl) acrylamide (compound FLZ), a novel synthetic analogue of squamosamide, on the dysfunction of rat brain mitochondria induced by AΒ 25-35 in vitro. Methods: Isolated rat brain mitochondria were incubated with aged AΒ 25-35 for 30 min in the presence and absence of FLZ (1-100 mol/L). The activities of key mitochondrial enzymes, the production of hydrogen peroxide (H 2 O 2) and superoxide anion (O 2-), and the levels of glutathione (GSH) in mitochondria were examined. Mitochondrial swelling and the release of cytochrome c from mitochondria were assessed by biochemical and Western blot methods, respectively. Results: Incubation of mitochondria with aged AΒ 25-35 inhibited the activities of α-ketoglutarate dehydrogenase (α-KGDH), pyruvate dehydrogenase (PDH) and respiratory chain complex IV. It also resulted in increased H 2 O 2 and O 2- production, and decreased the GSH level in mitochondria. Furthermore, it induced mitochondrial swelling and cytochrome c release from the mitochondria. The addition of FLZ (100 mol/L) prior to treatment with AΒ 25-35 significantly prevented these toxic effects of AΒ 25-35 on the mitochondria. Conclusion: FLZ has a protective effect against AΒ 25-35-induced mitochondrial dysfunction in vitro. © 2009 CPS and SIMM.