Unknown,Transcriptomics,Genomics,Proteomics

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Global transcriptomic profiling of lactacystin-mediated neuronal death


ABSTRACT: Inhibition of proteasome degradation pathway has been implicated in neuronal cell death leading to neurodegenerative diseases such as ParkinsonM-bM-^@M-^Ys disease and AlzheimerM-bM-^@M-^Ys 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 M-NM-

ORGANISM(S): Mus musculus

SUBMITTER: Minghui Jessica Chen 

PROVIDER: E-GEOD-22465 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Up-regulation of endoplasmic reticulum stress-related genes during the early phase of treatment of cultured cortical neurons by the proteasomal inhibitor lactacystin.

Choy Meng Shyan MS   Chen Minghui Jessica MJ   Manikandan Jayapal J   Peng Zhao Feng ZF   Jenner Andrew M AM   Melendez Alirio J AJ   Cheung Nam Sang NS  

Journal of cellular physiology 20110201 2


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. We and others demonstrated that treatment of cortical neurons with the proteasomal inhibitor lactacystin leads to apoptosis. 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 significance of  ...[more]

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