Bcl-2 overexpression attenuates dopamine-induced apoptosis in an immortalized neural cell line by suppressing the production of reactive oxygen species.
Parkinson's disease is a neurodegenerative disease that is consequent to the loss of brain dopamine (DA) cells. These abnormalities are thought, in part, to be a manifestation of increased free radical production during the metabolism of catecholamines. The antiapoptic agent, bcl-2, has been shown to protect cells against the toxic effects of reactive oxygen species (ROS). Thus, we tested whether bcl-2 could attenuate the toxic effects of DA on immortalized neural cells. Our results show that DA caused dose-dependent cell death. The use of confocal microscopy and flow cytometry demonstrated that DA caused cell death through an apoptotic process. Moreover, DA caused a marked increase in ROS in these cells. Furthermore, overexpression of bcl-2 caused significant protection against DA-induced apoptosis. These results are discussed in terms of their support for a role of bcl-2 in the development of Parkinson's disease.
Cadet
J L
JL
Molecular Neuropsychiatry Section, NIH/NIDA, Intramural Research Program, Baltimore, Maryland 21224, USA. jcadet@intra.nida.nih.gov
Harrington
B
B
Ordonez
S
S
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D002316:Cardiotonic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D004298:Dopamine