In PC12 cells neurotoxicity induced by methamphetamine is related to proteasome inhibition.
Neurodegenerative disorders are featured by a variety of pathological hallmarks, and very often they are characterized by neuronal inclusions in specific brain nuclei. Occurrence of neuronal inclusions has been often related to the onset of cell death. Recent studies demonstrated that amphetamine derivatives produce intracellular inclusions, which are reminiscent of those occurring in degenerative disorders. In the present article, we analyzed the correlation between neuronal inclusions and cell death using methamphetamine (METH) in PC12 cell cultures. We found that the dose necessary to induce cell death is higher compared with that required to induce inclusions formation. Our results demonstrate a dissociation between formation of inclusion bodies and cell death suggesting that neuronal inclusions do not necessarily lead to cell death. The conclusions of the present article suggest that the onset of inclusion bodies represents a slight consequence of toxicity, which requires a prolonged cell viability to take place.
Lazzeri
Gloria
G
Department of Human Morphology and Applied Biology, University of Pisa, Via Roma, 55, 56126 Pisa, Italy.
Lenzi
Paola
P
Gesi
Marco
M
Ferrucci
Michela
M
Fulceri
Federica
F
Ruggieri
Stefano
S
Bruno
Valeria
V
Fornai
Francesco
F
D000818:Animals; D016923:Cell Death; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D002479:Inclusion Bodies / Q000187:drug effects* / Q000502:physiology; D008694:Methamphetamine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
D015259:Dopamine Agents; D008694:Methamphetamine; D046988:Proteasome Endopeptidase Complex