Inhibition of neuronal apoptosis by a metalloporphyrin superoxide dismutase mimic.
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.
Department of Medicine, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver 80206, USA.
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008665:Metalloporphyrins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D051381:Rats / Q000196:embryology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019311:Staurosporine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology
D016166:Free Radical Scavengers; D008665:Metalloporphyrins; C064769:N-acetylsphingosine; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D013482:Superoxide Dismutase; D019311:Staurosporine; D013110:Sphingosine