d with other peripheral tissues. In SH-SY5Y cultures, pretreatment with 10 μg/ml of phloroglucinol attenuates the cytotoxicity of hydrogen peroxide. In addition, when assessed with 2′,7′-dichlorofluorescein diacetate dye, the increase in reactive oxygen species (ROS) induced by hydrogen peroxide was significantly reduced by pretreatment with phloroglucinol. ROS is known to cause lipid peroxidation of the cell membranes, the carbonylation of intracellular proteins, and DNA damage, which can lead to various cellular dysfunctions and eventually cellular death. We found that pretreatment with phloroglucinol down-regulated the levels of 8-isoprostane, protein carbonylation, and 8-hydroxy deoxyguanine caused by hydrogen peroxide treatment in SH-SY5Y cells. These results indicate that phloroglucinol exerts protective effects against oxidative stress-induced cell damage in SH-SY5Y cells.22:T469,Neuregulin-1 (NRG1) plays important roles in the development and plasticity of the brain, and it is also reported to have potent neuroprotective properties. We previously reported that NRG1 has neuroprotective actions against Swedish amyloid precursor protein-induced neurotoxicity. In addition to the amyloid beta peptide, other metabolites of amyloid precursor protein (APP) such as the C-terminal fragments of APP (APP-CTs) have been reported to possess cytotoxic effects in neuronal cells. In this study, we investigated whether NRG1 exerts neuroprotective effects against APP-CTs and attempted to determine its neuroprotective mechanisms. NRG1 attenuated the neurotoxicities induced by the expression of APP-CTs in neuronal cells. NRG1 also reduced the accumulation of reactive oxygen species and attenuated mitochondrial membrane potential loss induced by APP-CTs. In addition, NRG1 upregulated the expression of the anti-apoptotic protein Bcl-2. This effect was blocked by the inhibition of ErbB4, a key NRG1 receptor. Taken together, these results demonstrate the neuroprotective potential of NRG1 in Alzheimer's disease.23:T527,Excitatory amino acid carrier 1 (EAAC1) is an important subtype of excitatory amino acid transporters (EAATs) and is the route for neuronal cysteine uptake. CoCl₂ is not only a hypoxia-mimetic reagent but also an oxidative stress inducer. Here, we found that CoCl₂ induced significant EAAC1 overexpression in SH-SY5Y cells and the hippocampus of mice. Transient transfection of EAAC1 reduced CoCl₂-induced cytotoxicity in SH-SY5Y cells. Based on this result, upregulation of EAAC1 expression by CoCl₂ is thought to represent a compensatory response against oxidative stress in an acute hypoxic state. We further demonstrated that pretreatment with Neuregulin-1 (NRG1) rescued CoCl₂-induced upregulation of EAAC1 and tau expression. NRG1 plays a protective role in the CoCl₂-induced accumulation of reactive oxygen species (ROS) and reduction in antioxidative enzyme (SOD and GPx) activity. Moreover, NRG1 attenuated CoCl₂-induced apoptosis and cell death. NRG1 inhibited the CoCl₂-induced release of cleaved caspase-3 and reduction in Bcl-X_L levels. Our novel finding suggests that NRG1 may play a protective role in hypoxia through the inhibition of oxidative stress and thereby maintain normal EAAC1 expression levels.

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