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We discovered by microarray analysis that lactacystin treatment modulates the expression of both potentially neuroprotective as well as pro\u2010apoptotic genes in neurons. However, the significance of the genes which upon transcriptional modulation contributed to proteasomal inhibition\u2010induced apoptosis, remained unidentified. By employing microarray analysis to decipher the time\u2010dependent changes in transcription of these genes in cultured cortical neurons, we discovered different groups of genes were transcriptionally regulated in the early and late phase of lactacystin\u2010induced cell death. In the early phase, several neuroprotective genes such as those encoding the proteasome subunits and ubiquitin\u2010associated enzymes, as well as the heat\u2010shock proteins (HSP) were up\u2010regulated. However, the pro\u2010apoptotic endoplasmic reticulum (ER) stress\u2010associated genes were also up\u2010regulated at the early phase of lactacystin\u2010induced neuronal cell death. In the late phase, genes encoding antioxidants and calcium\u2010binding proteins were up\u2010regulated while those associated with cholesterol biosynthesis were down\u2010regulated. The data suggest that ER stress may participate in mediating the apoptotic responses induced by proteasomal inhibition. The up\u2010regulation of the neuroprotective antioxidant genes and calcium\u2010binding protein genes and down\u2010regulation of the cholesterol biosynthesis genes in the later phase are likely consequences of stimulation of the pro\u2010apoptotic signaling pathways in the early phase of lactacystin treatment. J. Cell. Physiol. 226: 494\u2013510, 2011. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22359","type":"journal-article","created":{"date-parts":[[2010,8,3]],"date-time":"2010-08-03T15:15:43Z","timestamp":1280848543000},"page":"494-510","source":"Crossref","is-referenced-by-count":22,"title":["Up\u2010regulation of endoplasmic reticulum stress\u2010related genes during the early phase of treatment of cultured cortical neurons by the proteasomal inhibitor lactacystin"],"prefix":"10.1002","volume":"226","author":[{"given":"Meng Shyan","family":"Choy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghui Jessica","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayapal","family":"Manikandan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao 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