Dose-dependent induction of apoptosis by R-apomorphine in CHO-K1 cell line in culture.
A variety of mechanisms have been proposed as explanations for the distinctive neuropathology of Parkinson's disease, such as increased iron levels, increased oxidant stress or decreased antioxidant defences. The vulnerability of dopamine-containing neurons towards cell death has attracted much attention to the dopamine molecule itself as one of the probable neurotoxic factors leading to neurodegeneration. The similarity between apomorphine and dopamine with regards to their chemical, pharmacological and toxicological properties provided a basis for investigating the nature of the toxicity of the former agent. In this study the CHO-K1 cell line was exposed to different concentrations of apomorphine, and markers of cell death and apoptosis were studied. Apomorphine reduced cell proliferation in a dose-dependent fashion after 72 h incubation. Furthermore, apomorphine induced dose-dependent cell death at concentrations of 10-50 microM. The CHO-K1 line showed specific markers of apoptosis such as the typical DNA laddering phenomenon on agarose gel, morphological changes of apoptotic nuclei as described by in situ end labelling, and annexin binding. These data strongly suggest that apomorphine, like dopamine, elicits its cytotoxic effect with an apoptotic mechanism.
Pardini
Carla
C
Department of Neuroscience, University of Pisa, Via Roma 55 - 56126 Pisa, Italy.
Vaglini
Francesca
F
Galimberti
Sara
S
Corsini
Giovanni U
GU
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016466:CHO Cells / Q000166:cytology / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D011954:Receptors, Dopamine / Q000502:physiology; D013237:Stereoisomerism
D011954:Receptors, Dopamine; D001058:Apomorphine