METHAMPHETAMINE INDUCES APOPTOSIS IN IMMORTALIZED NEURAL CELLS - PROTECTION BY THE PROTOONCOGENE, BCL-2

Methamphetamine (METH) is an amphetamine analog that produces degenera tion of the dopaminergic system in mammals. The neurotoxic effects of the drug are thought to be mediated by oxygen-based free radicals. In the present report, we have used immortalized neural cells obtained fr om rat mesencephalon in order to further assess the role of oxidative stress in METH-induced neurotoxicity. We thus tested if the anti-death proto-oncogene, bcl-2, could protect against METH-induced cytotoxicit y. METH caused dose-dependent loss of cellular viability in control ce lls while bcl-2-expressing cells were protected against these deleteri ous effects. Using flow cytometry, immunofluorescent staining, and DNA electrophoresis, we also show that METH exposure can cause DNA strand breaks, chromatin condensation, nuclear fragmentation, and DNA ladder ing. AU these changes were prevented by bcl-2 expression. These observ ations provide further support for the involvement of oxidative stress in the toxic effects of amphetamine analogs. They also document that METH-induced cytotoxicity is secondary to apoptosis. These findings ma y be of relevance to the cause(s) of Parkinson's disease which involve s degeneration of the nigrostriatal dopaminergic pathway. (C) 1997 Wil ey-Liss, Inc.