Involvement of protein kinase C and E2F-5 in euxanthone-induced neurite differentiation of neuroblastoma

Wai Yan Ha, Pui Kei Wu, Tsz Wai Kok, Kar Wah Leung, Nai Ki MAK, Patrick Y K YUE, Sai Ming Ngai, Sau Na Tsai, Ricky N S WONG*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

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) α/βI 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.

Original languageEnglish
Pages (from-to)1393-1401
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume38
Issue number8
DOIs
Publication statusPublished - 2006

Scopus Subject Areas

  • Biochemistry
  • Cell Biology

User-Defined Keywords

  • Differentiation
  • E2F-5 transcription factor
  • Euxanthone
  • Neurite outgrowth
  • Neuroblastoma

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