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 th e loss of brain dopamine (DA) cells. These abnormalities are thought, in pa rt, to be a manifestation of increased free radical production during the m etabolism of catecholamines. The antiapoptic agent, bcl-2, has been shown t o 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 i mmortalized neural cells. Our results show that DA caused dose-dependent ce ll death. The use of confocal microscopy and flow cytometry demonstrated th at 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 develop ment of Parkinson's disease. (C) 2000 Wiley-Liss, Inc.