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Involvement of caspases and calpains in cerebrocortical neuronal cell death is stimulus-dependent

Jonathan D Moore1, Nancy J Rothwell, Rosemary M Gibson

  • 1School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT.

British Journal of Pharmacology
|February 28, 2002
PubMed

Insights

Caspases and calpains mediate neuronal apoptosis. This study found stimulus-dependent activation of these enzymes in primary cerebrocortical neurons, with varying roles in cell death execution.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Caspases and calpains are key enzymes involved in programmed cell death (apoptosis).
  • Understanding their specific roles in neuronal apoptosis is crucial for neurodegenerative disease research.
  • Primary cerebrocortical neurons (CCNs) are a relevant model for studying neuronal cell death.

Purpose of the Study:

  • To investigate the involvement of caspases and calpains in primary CCN death induced by various apoptotic stimuli.
  • To elucidate stimulus-dependent activation pathways of these proteases in neurons.

Main Methods:

  • Primary rat CCNs were treated with staurosporine, C2-ceramide, camptothecin, hydrogen peroxide, or NMDA.
  • Caspase and calpain activity were measured using fluorogenic substrates and alpha-fodrin cleavage.
  • Cell death was quantified using lactate dehydrogenase (LDH) assay in the presence of caspase (Baf) and calpain (CP) inhibitors.

Main Results:

  • Staurosporine, ceramide, and camptothecin induced caspase activation (especially caspase-3) and cell death, suppressed by Baf.
  • Hydrogen peroxide activated caspases -1, -6, and -8, with cell death partially inhibited by calpeptin.
  • NMDA induced cell death without significant caspase activation, and all stimuli activated calpains, but only H2O2-induced death was affected by calpeptin.

Conclusions:

  • Neuronal apoptosis involves stimulus-specific activation pathways for caspases and calpains.
  • The executionary role of caspases and calpains in CCN death is dependent on the inducing agent.
  • Distinct signaling routes contribute to neuronal cell death, highlighting therapeutic targets.

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