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Involvement of protein kinase C and E2F-5 in euxanthone-induced neurite differentiation of neuroblastoma. Int J Biochem Cell Biol 2006;38(8):1393-401

Date

03/21/2006

Pubmed ID

16546434

DOI

10.1016/j.biocel.2006.02.002

Scopus ID

2-s2.0-33646192904   17 Citations

Abstract

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.

Author List

Ha WY, Wu PK, Kok TW, Leung KW, Mak NK, Yue PY, Ngai SM, Tsai SN, Wong RN

Author

Pui Kei Wu PhD Instructor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Carbazoles
Cell Differentiation
Cell Line, Tumor
E2F Transcription Factors
Electrophoresis, Gel, Two-Dimensional
Gene Silencing
Indoles
Neurites
Neuroblastoma
Protein Kinase C
Protein Kinase Inhibitors
Proteomics
Proto-Oncogene Proteins c-akt
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Xanthones
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a