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Murine cortical cell cultures exposed to 0.1\u2003\u00b5<jats:sc>m<\/jats:sc> MG132 underwent widespread neuronal apoptosis and showed partial inhibition of proteasome activity down to 30\u201350%. Interestingly, administration of 1\u201310\u2003\u00b5<jats:sc>m<\/jats:sc> MG132 almost completely blocked proteasome activity but resulted in reduced neuronal apoptosis. Similar results were produced in cortical cultures exposed to other proteasome inhibitors, proteasome inhibitor I and lactacystin. Administration of 0.1\u2003\u00b5<jats:sc>m<\/jats:sc> MG132 led to activation of a mitochondria\u2010dependent apoptotic signaling cascade involving cytochrome <jats:italic>c<\/jats:italic>, caspase\u20109, caspase\u20103 and degradation of tau protein; such activation was markedly reduced with 10\u2003\u00b5<jats:sc>m<\/jats:sc> MG132. High doses of MG132 prevented the degradation of inhibitor of apoptosis proteins (IAPs) cIAP and X chromosome\u2010linked IAP, suggesting that complete blockade of proteasome activity interferes with progression of apoptosis. In support of this, addition of high doses of proteasome inhibitors attenuated apoptosis of cortical neurons deprived of serum. Taken together, the present results indicate that inhibition of proteasome activity can induce or prevent neuronal cell apoptosis through regulation of mitochondria\u2010mediated apoptotic pathways and IAPs.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2005.03393.x","type":"journal-article","created":{"date-parts":[[2005,9,2]],"date-time":"2005-09-02T09:36:58Z","timestamp":1125653818000},"page":"684-694","source":"Crossref","is-referenced-by-count":28,"title":["Induction and attenuation of neuronal apoptosis by proteasome inhibitors in murine cortical cell cultures"],"prefix":"10.1111","volume":"95","author":[{"given":"Jaehong","family":"Suh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Ae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byoung Joo","family":"Gwag","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,9,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.292.5521.1552"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)02231-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biophys.28.1.295"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-02-00589.2000"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2000.0335"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1016\/S0166-2236(00)01998-6","article-title":"The role of the ubiquitin\u2013proteasomal pathway in Parkinson's disease and other neurodegenerative disorders","volume":"24","author":"Chung K. 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