Comparative global transcriptomic profiling of low and high concentration of lactacystin-mediated neuronal death

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. However, Meiners et al., 2003 suggested that low dose of lactacystin induces a concerted expression of proteasome genes and de novo formation of proteasomes. We discovered by microarray analysis that lactacystin treatment induces a dose-dependent biphasic modulation of both potentially neuroprotective as well as pro-apoptotic genes in neurons. Microarray analysis was carried out using 24 Illumina mouse Ref8V1.1 genechip arrays. The assignment of the arrays was as follows: Controls (n=6); exposure to 1 μM (High) lactacystin for 5h, 8h, 15h and 24 h (n=3 respectively) and 0.1uM (Low) for 15h and 24h (n=3 respectively).