Involvement of the JNK activation in terbinafine-induced p21 up-regulation and DNA synthesis inhibition in human vascular endothelial cells

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3 Citations (Scopus)

Abstract

Previously, we demonstrated that the extracellular signal-regulated kinase (ERK)-mediated pathway contributes to the terbinafine (TB)-induced increases of p21 and p53 protein level as well as decrease of DNA synthesis in human umbilical venous endothelial cells (HUVEC). The aim of this study is to examine the involvement of c-Jun NH2-terminal kinase (JNK) in the TB-induced increase of p21 protein level and DNA synthesis inhibition. Western blot analysis and kinase assay demonstrated that TB treatment increased both the protein level and the kinase activity of JNK1/2 in HUVEC. Transfection of HUVEC with JNK1 dominant negative (DN-JNK1) prevented the TB-induced increases of p21 and p53 protein level and decrease of DNA synthesis, suggesting that JNK1/2 activation is involved in the TB-induced cell cycle arrest in HUVEC. Moreover, over-expression of mitogen-activated protein kinase (MEK)-1 prevented the TB-induced increase of JNK1/2 protein levels, suggesting that MEK-1 is an upstream inhibitor of JNK. Transfection of HUVEC with DN-JNK1 prevented the TB-induced inhibition of ERK phosphorylation, suggesting that JNK1/2 might serve as a negative regulator of ERK. Taken together, our results suggest that JNK activation is involved in the TB-induced inhibition of ERK phosphorylation, p53 and p21 up-regulation and DNA synthesis inhibition in HUVEC.

Original languageEnglish
Pages (from-to)860-866
Number of pages7
JournalJournal of Cellular Biochemistry
Volume108
Issue number4
DOIs
Publication statusPublished - Nov 1 2009

Keywords

  • ERK
  • JNK
  • p21
  • p53
  • Terbinafine

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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