Abstract:
:We previously reported that NSC606985, a new camptothecin analog, induces apoptosis of acute myeloid leukemic cells, which is triggered by proteolytic activation of protein kinase C delta (PKC delta). Here, we performed quantitative proteomic analysis of NSC606985-treated and untreated leukemic U937 cells with two-dimensional fluorescence difference gel electrophoresis (2-D DIGE) in combination with matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem mass spectrometry. Thirty-three proteins were found to be deregulated. Then, we focused on N-myc downstream regulated gene 1 (NDRG1) down-regulated during apoptosis induction. The results demonstrated that the down-regulation of NDRG1 protein but not its mRNA was an early event prior to proteolytic activation of PKC delta in U937 cells under treatments of NSC606985 as well as other camptothecin analogs. With the ectopic expression of NDRG1, the proteolytic activation of PKC delta in NSC606985-treated leukemic cells was delayed and the cells were less sensitive to apoptosis. On the contrary, the suppression of NDRG1 expression by specific small interfering RNA significantly enhanced NSC606985-induced activation of PKC delta and apoptosis of U937 cells. In summary, our study suggests that the down-regulation of NDRG1 is involved in proteolytic activation of PKC delta during apoptosis induction, which would shed new light on the understanding the apoptotic process initiated by camptothecin.
journal_name
Proteomicsjournal_title
Proteomicsauthors
Zheng Y,Wang LS,Xia L,Han YH,Liao SH,Wang XL,Cheng JK,Chen GQdoi
10.1002/pmic.200800031subject
Has Abstractpub_date
2009-04-01 00:00:00pages
2064-75issue
8eissn
1615-9853issn
1615-9861journal_volume
9pub_type
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