HMG-CoA reductase inhibitor induces a transient activation of high affinity nerve growth factor receptor, Trk, and morphological differentiation with fatal outcome in PC 12 cells

Takanori Kumano, Tatsuro Mutoh, Hiroto Nakagawa, Masaru Kuriyama

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The present study was aimed at investigating the possible toxicity of simvastatin on a neuronal cell line, PC12 cells. Simvastatin clearly induced a transient morphological differentiation as evidenced by the occurrence of neurite outgrowth with a transient activation of the high affinity nerve growth factor receptor, Trk, but died at 36 h after its addition. Tyrosine autophosphorylation of the Trk protein also disappeared at 36 h after addition. During the morphological differentiation, NGF mRNA expression was upregulated transiently and returned to the basal level at 36 h after addition of simvastatin. These results suggest that simvastatin is neurotoxic and PC12 cells elicited a protective response, involving a transient activation of a Trk-mediated intracellular signal transduction pathway by an autocrine secretion of NGF, although these responses did not persist against pro-apoptotic signals and resulted in an apoptosis of the PC12 cells.

Original languageEnglish
Pages (from-to)169-172
Number of pages4
JournalBrain Research
Volume859
Issue number1
DOIs
Publication statusPublished - 17-03-2000

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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