Drugs of abuse induce apoptotic features in PC12 cells.
Drugs of abuse induce the release of dopamine in the central nervous system, particularly in the mesolimbic-mesocortical pathway. As dopamine may act as a neurotoxin, in this study, we analyzed the effects of the drugs of abuse, cocaine, heroin, and amphetamine, on the neurodegeneration of PC12 cells, a dopaminergic cell line, by evaluating the activity of caspase-3 and mitochondrial cytochrome c release. All the drugs were shown to induce caspase-3 activation, similarly to staurosporine, a classical inducer of apoptotic cell death. Furthermore, like staurosporine, the drugs of abuse induced a decrease in mitochondrial cytochrome c content, suggesting the involvement of the mitochondrial apoptotic pathway.
Oliveira
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Institute of Biochemistry, Faculty of Medicine and Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, 3004-504 Coimbra, Portugal.
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Macedo
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Oliveira
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D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D003932:Heroin / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D019966:Substance-Related Disorders
D003932:Heroin; D045304:Cytochromes c; D000661:Amphetamine; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003042:Cocaine