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Cyclosporine A- and FK506-induced apoptosis in PC12 cells

T Takadera1, Y Sakamoto, Y Hizume

  • 1Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa, Ishikawa, 920-1148, Japan. t-takadera@hokuriku-u.ac.jp

Cell Biology and Toxicology
|March 27, 2007
PubMed

Insights

Cyclosporine A (CsA) and FK506 trigger apoptosis in PC12 cells via caspase-3 activation. Glycogen synthase kinase-3 (GSK-3) activation is involved in this process, and its inhibition prevents cell death.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pharmacology

Background:

  • Cyclosporine A (CsA) and FK506 are immunosuppressants known to induce cell death.
  • Apoptosis, or programmed cell death, is a critical cellular process.
  • PC12 cells are a neuronal cell line frequently used in apoptosis research.

Purpose of the Study:

  • To investigate the role of glycogen synthase kinase-3 (GSK-3) in CsA- and FK506-induced apoptosis.
  • To determine if GSK-3 activation is a key mediator in the apoptotic pathway triggered by these compounds.

Main Methods:

  • PC12 cells were treated with CsA and FK506 to induce apoptosis.
  • Morphological changes indicative of apoptosis were observed.
  • The activation of caspase-3 was measured.
  • GSK-3 inhibitors (alsterpaullone, SB216763) were used to block GSK-3 activity.
  • Nerve growth factor (NGF) was used as a protective agent.

Main Results:

  • CsA and FK506 induced significant apoptotic cell death in PC12 cells, characterized by cell shrinkage and nuclear fragmentation.
  • Nerve growth factor (NGF) completely protected PC12 cells from CsA- and FK506-induced apoptosis.
  • Caspase-3 activation was observed concurrently with CsA- and FK506-induced cell death and was inhibited by NGF.
  • Inhibition of GSK-3 using alsterpaullone and SB216763 effectively prevented CsA- and FK506-induced apoptosis.

Conclusions:

  • CsA and FK506 induce apoptosis in PC12 cells in a caspase-dependent manner.
  • GSK-3 activation plays a crucial role in the apoptotic process initiated by CsA and FK506 in PC12 cells.
  • Targeting GSK-3 may offer a therapeutic strategy to mitigate CsA- and FK506-induced cellular damage.

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