Genistein-induced neuronal differentiation is associated with activation of extracellular signal-regulated kinases and upregulation of p21 and N-cadherin

S. P. Hung, J. R. Hsu, C. P. Lo, H. J. Huang, J. P. Wang, S. T. Chen

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Neuronal differentiation in the mammalian CNS is driven by multiple events. When treated with retinoic acid (RA), hNTera-2 (NT-2) cells undergo postmitotic neuronal differentiation. Here, we show that a prolonged exposure of NT-2 cells with non-cytotoxic doses of genistein, a protein tyrosine kinase (PTK) inhibitor, induced differentiation of NT-2 cells. Additionally, genistein enhanced RA-induced neuronal differentiation by increasing the activation of extracellular signal-related kinase 1/2 (ERK1/2) via phosphorylation at Thr183 and Tyr185 in 3-7 days. Meanwhile, genistein also upregulated N-cadherin and p21 (a Cdk inhibitor), but downregulated proliferating cell nuclear antigen protein (PCNA). MEK1/2 inhibitors, such as PD98059 and U0126, reduced RA-induced ERK1/2 activity, but could not block the genistein effects. Our observations indicate that genistein-induced neuronal differentiation is not dependent of the MEK-ERK signaling cascade. Instead, genistein-upregulated ERK activation is likely due to this chemical's direct effect on chromosome and gene transcription, rather than its inhibition on tyrosine kinases. Failure of inhibition of ERK1/2 activation by the MEK1/2 inhibitors PD98059 and U0126 suggests presence of an unknown activator for ERK1/2 in neuronal cells.

Original languageEnglish
Pages (from-to)1061-1070
Number of pages10
JournalJournal of Cellular Biochemistry
Volume96
Issue number5
DOIs
Publication statusPublished - 2005 Dec 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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