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Title: The mechanisms of lactacystin-induced apoptosis of mouse primary cortical neurons
Keywords: Proteasome inhibition, lactacystin, apoptosis, PTEN, microarray, lipid profile
Issue Date: 9-Aug-2006
Citation: CHOY MENG SHYAN (2006-08-09). The mechanisms of lactacystin-induced apoptosis of mouse primary cortical neurons. ScholarBank@NUS Repository.
Abstract: Exposure of the proteasome inhibitor lactacystin to mouse primary cortical neurons induced apoptosis and caused the accumulation of tumor suppressor PTEN in the plasma membrane. However, microarray analysis of neurons exposed to lactacystin reveals the early up-regulation of genes in response to unfolded proteins and endoplasmic reticulum (ER) stress. A mechanism of apoptotic cell death through the abnormal accumulation of protein and ER stress is suggested. The lipid profile of the neural membrane reveals the accumulation of ceramides and N-acyl phosphatidylethanolamines (NAPEs) during lactacystin-induced apoptosis. The accumulation of NAPEs during apoptosis has not been reported previously. Epigallocatechin-3-gallate (EGCG), a naturally occurring proteasome inhibitor from green tea extract was able to induce apoptosis in cultured neurons at 25 A?M. At a lower concentration (1 A?M), EGCG was able to cause the up-regulation of genes encoding proteasome subunits and ubiquitin, suggesting a potential neuroprotective effect against neurodegeneration.
Appears in Collections:Ph.D Theses (Open)

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