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ERK1/2 inhibition increases dopamine release from differentiated PC12 cells

D V Zosen1, N A Dorofeeva1, E V Chernigovskaya1

  • 1Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez pr., 194223 St. Petersburg, Russia.

Neuroscience Letters
|July 4, 2018
PubMed

Insights

Inhibiting ERK1/2 kinases increases dopamine (DA) release from PC12 cells, suggesting a key role for these enzymes in regulating neurotransmitter secretion.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Dopamine (DA) release is crucial for neuronal function in the central nervous system (CNS).
  • Regulation of DA secretion involves protein kinases and synaptic proteins, but existing data are often contradictory.
  • Understanding these regulatory mechanisms is essential for deciphering neuronal communication.

Purpose of the Study:

  • To investigate the effect of inhibiting extracellular signal-regulated kinases 1/2 (ERK1/2) on DA secretion from differentiated PC12 cells.
  • To evaluate the correlation between kinase/synaptic protein activity and the level of released DA.
  • To elucidate the role of ERK1/2 in catecholamine release.

Main Methods:

  • PC12 cells were differentiated using nerve growth factor (NGF).
  • Differentiated cells were treated with U0126 (an ERK1/2 inhibitor) for 1, 2, and 4 hours.
  • Dopamine levels in the media were measured.
  • Protein kinase G (PKG) activity was assessed.
  • Phosphorylation of synapsin I and the content of SNAP25 were analyzed.

Main Results:

  • A significant accumulation of DA was observed in the media after 4 hours of U0126 treatment.
  • U0126 treatment was accompanied by an upregulation of PKG activity.
  • Analysis revealed a decreased phosphorylation level of synapsin I and reduced SNAP25 content.
  • These findings suggest ERK1/2 normally inhibits dopamine secretion.

Conclusions:

  • Extracellular signal-regulated kinases 1/2 (ERK1/2) play an inhibitory role in regulating catecholamine secretion.
  • The balance between protein kinase G (PKG) and ERK1/2 activity significantly impacts DA release from cells.
  • This study provides new insights into the complex regulation of dopamine release.
Keywords:
DopamineERK1/2PC12 cellsPKAPKGSNAP-25Synapsin IU0126

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