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Mitogen-activated protein kinase signaling is involved in suramin-induced neurite outgrowth in a neuronal cell line

Hiroyasu Nakata1

  • 1Department of Molecular Cell Signaling, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan. nakata@tmin.ac.jp

Biochemical and Biophysical Research Communications
|February 27, 2007
PubMed

Insights

Suramin, an anti-cancer drug, promotes nerve cell growth by activating the Src/ERK1/2 pathway. This process is negatively regulated by adenosine A2A receptors and cAMP signaling.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Suramin is an established antitrypanosomal drug with emerging roles in cancer therapy.
  • Previous research indicated suramin activates extracellular signal-regulated kinase (ERK1/2) signaling, but its physiological significance was unclear.

Purpose of the Study:

  • To investigate the role of suramin in neurite outgrowth in neuronal cells.
  • To elucidate the signaling pathways involved in suramin-induced neurite outgrowth.

Main Methods:

  • Utilized Neuro-2a cells, a neuronal cell line, to study suramin's effects.
  • Employed PD98059 (a mitogen-activated protein kinase kinase inhibitor) and adenosine A2A receptor activators to assess pathway involvement.
  • Investigated the role of Src family kinases in suramin signaling.

Main Results:

  • Suramin significantly enhanced neurite outgrowth and ERK1/2 activation in Neuro-2a cells.
  • Neurite outgrowth and ERK1/2 activation were inhibited by PD98059 and adenosine A2A receptor activation.
  • Inhibition of Src family kinases attenuated suramin-induced ERK1/2 activity and neurite outgrowth.

Conclusions:

  • Suramin activates the Src/ERK1/2 signaling pathway, promoting neurite outgrowth.
  • cAMP, via adenosine A2A receptor activation, negatively regulates this suramin-induced pathway.

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