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

研究成果: Article査読

18 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)169-172
ページ数4
ジャーナルBrain Research
859
1
DOI
出版ステータスPublished - 17-03-2000
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 分子生物学
  • 臨床神経学
  • 発生生物学

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