E-GEOD-22465 - Global transcriptomic profiling of lactacystin-mediated neuronal death
Released on 3 January 2012, last updated on 26 June 2012
Inhibition of proteasome degradation pathway has been implicated in neuronal cell death leading to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Pharmacological proteasomal inhibitors such as lactacystin can induce apoptosis in cultured mouse cortical neurons through the activation of caspase-3. Furthermore, proteasomal inhibitors are also reported to mediate deleterious alterations in cell cycle regulation, inflammatory processes and protein aggregation and trigger the cell death pathway. We discovered by microarray analysis that lactacystin treatment modulates the expression of both potentially neuroprotective as well as pro-apoptotic genes in neurons. However, the genes, upon transcriptional modulation, contribute to proteasomal inhibition-induced apoptosis, remains unidentified. By employing microarray analysis to decipher the time-dependent changes in transcription of these genes in cultured cortical neurons, we discovered different groups of genes were transcriptionally regulated at different phases of lactacystin-induced cell death. Microarray analysis was carried out using 10 murine genome U74A and U74Av2 Genechips array (Affymetrix, Santa Clara, CA). The assignment of the arrays (GeneChip) was as follows: Control at 24 h (n=2), 48 h (n=2); exposure to 1 μM lactacystin for 24 h (n=3) and 48 h (n=3).
transcription profiling by array
Minghui Jessica Chen <firstname.lastname@example.org>, Jayapal Manikandan, Minghui J Chen, Nam S Cheung, Zhao F Peng
Up-regulation of endoplasmic reticulum stress-related genes during the early phase of treatment of cultured cortical neurons by the proteasomal inhibitor lactacystin. Choy MS, Chen MJ, Manikandan J, Peng ZF, Jenner AM, Melendez AJ, Cheung NS. , Europe PMC 20683911