Article ID Journal Published Year Pages File Type
2202334 Neurochemistry International 2006 7 Pages PDF
Abstract

1-{3-[2-(1-Benzothiophen-5-yl)ethoxy]propyl}-3-azetidinol maleate (T-817MA), a novel neurotrophic agent, protects against amyloid-β peptide- or hydrogen peroxide-induced neuronal death. The exact mechanism of the neuroprotection is not known. This study examines the effects of T-817MA on oxidative stress-induced cytotoxicity in primary rat cortical neurons. Treatment with the NO donor sodium nitoroprusside (SNP) at 300 μM decreased cell viability and induced apoptotic cell death. SNP-induced neuronal toxicity was accompanied by a decrease in mitochondrial transmembrane potential without an increase in the expression of CHOP and GRP78 mRNAs, endoplasmic reticulum stress makers. T-817MA at 0.1 and 1 μM attenuated the neurotoxicity in a dose-dependent way and the protective effect required pretreatment for more than 8 h. T-817MA attenuated SNP-induced decrease in mitochondrial transmembrane potential. In addition, the agent reduced SNP-induced increase in mitochondrial reactive oxygen species (ROS) production. The effects of T-817MA on SNP-induced decrease in cell viability and SNP-induced increase in mitochondrial ROS production were blocked by cycloheximide. These results suggest that T-817MA improves SNP-induced mitochondrial dysfunction in cortical neurons in a newly synthesized protein-mediated mechanism and this effect contributes to its neuroprotective effect.

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