Dopamine induces apoptotic cell death of a catecholaminergic cell line derived from the central nervous system.
Dopamine produces a time- and dose-dependent increase in cell death in a clonal catecholaminergic cell line (CATH.a) derived from the central nervous system. Cell death also occurred after treatment with the catecholamines L-dihydroxyphenylalanine, norepinephrine, epinephrine, and isoproterenol, as well as the neurotoxic compound 6-hydroxydopamine. Cell death is not receptor mediated because selective noradrenergic and dopaminergic receptor agonists had no effect on CATH.a cell viability. Dopamine induces apoptotic cell death as indicated by DNA fragmentation measured by gel electrophoresis and by flow cytometric analysis. Apoptosis seems to be produced by dopamine autoxidation, because intracellular peroxides increase after dopamine treatment and cell death can be inhibited by catalase and N-acetylcysteine. N-acetylcysteine produced a dose-dependent decrease in dopamine-induced cell death; this correlated with a decrease in peroxide formation. In addition, antisense to the antioxidant protein bcl-2 increases the sensitivity of CATH.a cells to dopamine-induced cell death. These findings indicate that the oxidative products of dopamine cause neurotoxicity through apoptosis.
National Institute of Mental Health Neuroscience Center at Saint Elizabeths, Neuropsychiatry Branch, Washington, D.C. 20032, USA. masseraj@dirpc.nimh.nih.gov
J M
JM
Masserano
L
L
Gong
H
H
Kulaga
I
I
Baker
R J
RJ
Wyatt
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms; D002395:Catecholamines / Q000494:pharmacology / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects; D002490:Central Nervous System / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000633:toxicity*; D051379:Mice; D008822:Mice, Transgenic; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010545:Peroxides / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D002395:Catecholamines; D016376:Oligonucleotides, Antisense; D010545:Peroxides; D019253:Proto-Oncogene Proteins c-bcl-2; D004298:Dopamine