PMID- 16546434 OWN - NLM STAT- MEDLINE DCOM- 20060905 LR - 20091119 IS - 1357-2725 (Print) IS - 1357-2725 (Linking) VI - 38 IP - 8 DP - 2006 TI - Involvement of protein kinase C and E2F-5 in euxanthone-induced neurite differentiation of neuroblastoma. PG - 1393-401 AB - Euxanthone, a neuritogenic agent isolated from the medicinal herb Polygala caudata, has been shown to induce morphological differentiation and neurite outgrowth in murine neuroblastoma Neuro 2a cells (BU-1 subclone). In order to elucidate the underlying mechanisms of euxanthone-induced neurite outgrowth, a proteomic approach was employed. In the present study, two dimensional (2-D) gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) mass spectrometry were performed to investigate the alterations in protein expression profile of euxanthone-treated BU-1 cells. Fourteen identified proteins were changed in expression levels after induction of neurite growth. These proteins included participants in transcription and cell cycle regulation, calcium influx and calcium signaling, fatty acid metabolism, cytoskeleton reorganization, casein kinase signal transduction, putative transbilayer amphipath transport and protein biosynthesis. Among the 14 identified proteins, E2F transcription factor 5 (E2F-5) was significantly up-regulated after euxanthone treatment. Go6976, a protein kinase C (PKC) alpha/betaI inhibitor, was found to inhibit neuritogenesis and expression of E2F-5 in the euxanthone-treated BU-1 cells, while SH-6, the Akt/PKB inhibitor, had no inhibitory effect. The gene silencing of E2F-5 by small interfering RNA (siRNA) was found to abolish the euxanthone-induced neurite outgrowth. In conclusion, these results indicated that the transcription factor E2F-5 was actively involved in the regulation of euxanthone-induced neurite outgrowth via PKC pathway. FAU - Ha, Wai Yan AU - Ha WY AD - Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China. FAU - Wu, Pui Kei AU - Wu PK FAU - Kok, Tsz Wai AU - Kok TW FAU - Leung, Kar Wah AU - Leung KW FAU - Mak, Nai Ki AU - Mak NK FAU - Yue, Patrick Ying Kit AU - Yue PY FAU - Ngai, Sai Ming AU - Ngai SM FAU - Tsai, Sau Na AU - Tsai SN FAU - Wong, Ricky Ngok Shun AU - Wong RN LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060302 PL - Netherlands TA - Int J Biochem Cell Biol JT - The international journal of biochemistry & cell biology JID - 9508482 RN - 0 (Carbazoles) RN - 0 (E2F Transcription Factors) RN - 0 (Indoles) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Xanthones) RN - 136194-77-9 (Go 6976) RN - 529-61-3 (euxanthone) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - Animals MH - Carbazoles/pharmacology MH - Cell Differentiation/*drug effects MH - Cell Line, Tumor MH - E2F Transcription Factors/genetics/*metabolism MH - Electrophoresis, Gel, Two-Dimensional MH - Gene Silencing MH - Indoles/pharmacology MH - Neurites/drug effects/*metabolism MH - Neuroblastoma/metabolism/pathology MH - Protein Kinase C/antagonists & inhibitors/*metabolism MH - Protein Kinase Inhibitors/pharmacology MH - Proteomics/methods MH - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/metabolism MH - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization MH - Xanthones/*pharmacology EDAT- 2006/03/21 09:00 MHDA- 2006/09/06 09:00 CRDT- 2006/03/21 09:00 PHST- 2005/10/06 00:00 [received] PHST- 2006/01/25 00:00 [revised] PHST- 2006/02/06 00:00 [accepted] PHST- 2006/03/21 09:00 [pubmed] PHST- 2006/09/06 09:00 [medline] PHST- 2006/03/21 09:00 [entrez] AID - S1357-2725(06)00039-2 [pii] AID - 10.1016/j.biocel.2006.02.002 [doi] PST - ppublish SO - Int J Biochem Cell Biol. 2006;38(8):1393-401. doi: 10.1016/j.biocel.2006.02.002. Epub 2006 Mar 2.