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Methamphetamine induces apoptosis in immortalized neural cells: Protection by the Proto‐Oncogene, bcl‐2
Author(s) -
Cadet Jean Lud,
Ordonez Sonia V.,
Ordonez Jose V.
Publication year - 1997
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199702)25:2<176::aid-syn8>3.0.co;2-9
Subject(s) - neurotoxicity , meth , dna laddering , methamphetamine , dopaminergic , oxidative stress , apoptosis , cytotoxicity , dna damage , programmed cell death , chemistry , microbiology and biotechnology , neurodegeneration , dna fragmentation , viability assay , biology , pharmacology , biochemistry , neuroscience , toxicity , dopamine , dna , pathology , medicine , in vitro , disease , monomer , polymer , organic chemistry , acrylate
Methamphetamine (METH) is an amphetamine analog that produces degeneration 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 from 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 cytotoxicity. METH caused dose‐dependent loss of cellular viability in control cells while bcl‐2‐expressing cells were protected against these deleterious 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 laddering. All these changes were prevented by bcl‐2 expression. These observations 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 may be of relevance to the cause(s) of Parkinson's disease which involves degeneration of the nigrostriatal dopaminergic pathway. Synapse 25:176–184, 1997. © 1997 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.