Inhibition of neuronal apoptosis by a metalloporphyrin superoxide dismutase mimic

J Neurochem. 1998 Sep;71(3):1068-74. doi: 10.1046/j.1471-4159.1998.71031068.x.


The objective of this study was to determine whether free radicals play a pathogenic role in neuronal apoptosis. The ability of Mn(III) tetrakis(benzoic acid) porphyrin (MnTBAP), a superoxide dismutase mimic, to inhibit staurosporine-induced neuronal apoptosis was tested in mixed cerebrocortical cultures. Staurosporine produced concentration-dependent cell death that was markedly inhibited by MnTBAP. Immunocytochemical analyses of cultures for neuron- and astrocyte-specific markers revealed that high concentrations of staurosporine induced the death of both neurons and astrocytes; both cell types were protected by MnTBAP. A less active congener of MnTBAP failed to protect cells against staurosporine-induced apoptosis. MnTBAP also protected cortical cultures against ceramide-induced apoptosis. These results support a role for oxidative stress in neuronal apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Astrocytes / drug effects
  • Astrocytes / physiology
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Coculture Techniques
  • Free Radical Scavengers / pharmacology*
  • Metalloporphyrins / pharmacology*
  • Neurons / drug effects*
  • Neurons / physiology*
  • Rats / embryology
  • Sphingosine / analogs & derivatives
  • Sphingosine / antagonists & inhibitors
  • Sphingosine / pharmacology
  • Staurosporine / antagonists & inhibitors
  • Staurosporine / pharmacology
  • Superoxide Dismutase / pharmacology


  • Free Radical Scavengers
  • Metalloporphyrins
  • N-acetylsphingosine
  • manganese(III)-tetrakis(4-benzoic acid)porphyrin
  • Superoxide Dismutase
  • Staurosporine
  • Sphingosine