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Midkine inhibits apoptosis via extracellular signal regulated kinase (ERK) activation in PC12 cells

K Owada1, N Sanjyo, T Kobayashi

  • 1Department of Neurology, Faculty of Medicine, Tokyo Medical and Dental Unviersity, Japan.

Journal of Medical and Dental Sciences
|August 6, 2002
PubMed

Insights

Midkine (MK) protects neuronal cells from apoptosis by activating the ERK pathway. This study clarifies the intracellular mechanisms underlying MK

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Midkine (MK) is a heparin-binding growth factor involved in neuronal development and survival.
  • The precise intracellular mechanisms of MK's neurotrophic actions remain unclear.

Purpose of the Study:

  • To investigate the intracellular signaling pathway activated by Midkine (MK).
  • To determine the role of the mitogen-activated protein kinase (MAPK) cascade in MK's neuroprotective effects.

Main Methods:

  • Established an apoptosis-induction system using the PC12 neuronal cell line.
  • Administered Midkine (MK) and PD98059 (a MAPKK inhibitor) to assess effects on apoptosis and ERK activation.

Main Results:

  • Midkine (MK) demonstrated dose-dependent rescue of PC12 cells from serum deprivation-induced apoptosis.
  • MK activated extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2).
  • Inhibition of ERK activation by PD98059 blocked MK's neuroprotective effect.

Conclusions:

  • Midkine (MK) exerts significant neuroprotective effects.
  • The ERK signaling pathway is crucial for mediating the neurotrophic actions of Midkine (MK).

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